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  1. Pharmacologic Therapies in Anticoagulation.

    PubMed

    Ferreira, Joana Lima; Wipf, Joyce E

    2016-07-01

    Anticoagulants are beneficial for prevention and treatment of venous thromboembolism and stroke prevention in atrial fibrillation. The development of target-specific oral anticoagulants is changing the landscape of anticoagulation therapy and created growing interest on this subject. Understanding the pharmacology of different anticoagulants is the first step to adequately treat patients with best available therapy while avoiding serious bleeding complications. This article reviews the pharmacology of the main anticoagulant classes (vitamin K antagonists, direct oral anticoagulants, and heparins) and their clinical indications based on evidence-based data currently available in the literature. PMID:27235611

  2. Oral Anticoagulant Therapy

    PubMed Central

    Gallus, Alexander S.; Wittkowsky, Ann; Crowther, Mark; Hylek, Elaine M.; Palareti, Gualtiero

    2012-01-01

    Background: The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management. Methods: We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban Results: The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal. Conclusions: There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban. PMID:22315269

  3. Anticoagulation Drug Therapy: A Review

    PubMed Central

    Harter, Katherine; Levine, Michael; Henderson, Sean O.

    2015-01-01

    Historically, most patients who required parenteral anticoagulation received heparin, whereas those patients requiring oral anticoagulation received warfarin. Due to the narrow therapeutic index and need for frequent laboratory monitoring associated with warfarin, there has been a desire to develop newer, more effective anticoagulants. Consequently, in recent years many novel anticoagulants have been developed. The emergency physician may institute anticoagulation therapy in the short term (e.g. heparin) for a patient being admitted, or may start a novel anticoagulation for a patient being discharged. Similarly, a patient on a novel anticoagulant may present to the emergency department due to a hemorrhagic complication. Consequently, the emergency physician should be familiar with the newer and older anticoagulants. This review emphasizes the indication, mechanism of action, adverse effects, and potential reversal strategies for various anticoagulants that the emergency physician will likely encounter. PMID:25671002

  4. The evolution of anticoagulant therapy

    PubMed Central

    Franchini, Massimo; Liumbruno, Giancarlo M.; Bonfanti, Carlo; Lippi, Giuseppe

    2016-01-01

    Arterial and venous thromboembolism are leading causes of morbidity and mortality around the world. For almost 70 years, heparins (unfractionated heparin and low molecular weight heparins) and vitamin K antagonists have been the leading therapeutic medical options for the treatment and prevention of thromboembolic disorders. Nevertheless, the many limitations of these traditional anticoagulants have fuelled the search for novel agents over the past 15 years, and a new class of oral anticoagulants that specifically target activated factor X and thrombin has been developed and is now commercially available. In this narrative review, the evolution of anticoagulant therapy is summarised, with a focus on newer oral anticoagulants. PMID:26710352

  5. Anticoagulant Therapy-Induced Gallbladder Hemorrhage after Cardiac Valve Replacement

    PubMed Central

    Cho, Seong Ho; Lee, Hae Young; Kim, Hyun Su

    2015-01-01

    Anticoagulation therapy is essential after cardiac valve surgery. However, spontaneous bleeding remains a major concern during anticoagulation therapy. Spontaneous gallbladder (GB) hemorrhage (hemobilia) is a rare occurrence during standard anticoagulation therapy. This report presents a case of GB hemorrhage that occurred shortly after initiating oral anticoagulant therapy in a patient who had undergone mitral valve replacement surgery. PMID:26665115

  6. Resuming anticoagulant therapy after intracerebral bleeding.

    PubMed

    Becattini, Cecilia; Sembolini, Agnese; Paciaroni, Maurizio

    2016-09-01

    The clinical benefit of resuming anticoagulant treatment after an anticoagulants-associated intracranial hemorrhage (ICH) is debated. No randomized trial has been conducted on this particular clinical issue. The risk of ICH recurrence from resuming anticoagulant therapy is expected to be higher after index lobar than deep ICH and in patients with not amendable risk factors for ICH. Retrospective studies have recently shown improved survival with resumption of treatment after index anticoagulants-associated ICH. Based on these evidences and on the risk for thromboembolic events without anticoagulant treatment, resumption of anticoagulation should be considered in all patients with mechanical heart valve prosthesis and in those with amendable risk factors for anticoagulants-associated ICH. Resumption with direct oral anticoagulants appears a reasonable option for non-valvular atrial fibrillation (NVAF) patients at moderate to high thromboembolic risk after deep ICH and for selected NVAF patients at high thromboembolic risk after lobar ICH. For VTE patients at high risk for recurrence, resumption of anticoagulation or insertion of vena cava filter should be tailored on the estimated risk for ICH recurrence. PMID:27260938

  7. Evidence-Based Management of Anticoagulant Therapy

    PubMed Central

    Schulman, Sam; Witt, Daniel M.; Vandvik, Per Olav; Fish, Jason; Kovacs, Michael J.; Svensson, Peter J.; Veenstra, David L.; Crowther, Mark; Guyatt, Gordon H.

    2012-01-01

    Background: High-quality anticoagulation management is required to keep these narrow therapeutic index medications as effective and safe as possible. This article focuses on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices. Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: Most practical clinical questions regarding the management of anticoagulation, both oral and parenteral, have not been adequately addressed by randomized trials. We found sufficient evidence for summaries of recommendations for 23 questions, of which only two are strong rather than weak recommendations. Strong recommendations include targeting an international normalized ratio of 2.0 to 3.0 for patients on vitamin K antagonist therapy (Grade 1B) and not routinely using pharmacogenetic testing for guiding doses of vitamin K antagonist (Grade 1B). Weak recommendations deal with such issues as loading doses, initiation overlap, monitoring frequency, vitamin K supplementation, patient self-management, weight and renal function adjustment of doses, dosing decision support, drug interactions to avoid, and prevention and management of bleeding complications. We also address anticoagulation management services and intensive patient education. Conclusions: We offer guidance for many common anticoagulation-related management problems. Most anticoagulation management questions have not been adequately studied. PMID:22315259

  8. [Cerebral vascular accidents in anticoagulant therapy].

    PubMed

    Woimant, F; Lecoz, P; Rajzbaum, G; Haguenau, M; Pépin, B

    1986-01-01

    Thirty-three patients hospitalized as they presented with cerebral vascular lesions during anticoagulant therapy (25 intracerebral hemorrhages, 7 subdural hematoma, and one ischemia lesion). Frequency of intra-cerebral hemorrhages along with anticoagulant therapy was about 11 p. 100, this of subdural hematoma ranged from 12 to 38 p. 100. Intra-cerebral hemorrhages failed to show any peculiar topography and volume was variable. A predisposing factor thus existed in about 50 p. 100 of cases: high blood pressure or arterial aneurysm. Previous cranial traumatism was only demonstrated in 48 p. 100 patients presenting with a subdural hematoma. Prognosis as for these intracranial hemorrhages might be compared to this of hemorrhagic lesions appearing under other etiologic conditions. Ischemia lesion was secondary to a severe thrombopenia to heparin. PMID:3813286

  9. Individualising Anticoagulant Therapy in Atrial Fibrillation Patients

    PubMed Central

    2016-01-01

    Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have emerged as alternatives to VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation. Four NOACS: dabigatran, apixaban, rivaroxaban and edoxaban, have received regulatory approval in Europe from the European Medicines Agency. Numerous factors can influence the decision to prescribe a NOAC, the most important of which are assessment of stroke and bleeding risks. Given the variation in design of the pivotal phase III clinical trials investigating the efficacy and safety of NOACs, and in the absence of head-to-head comparative data, it is impossible to recommend one NOAC over the other. However, NOACS offer the opportunity for individualised therapy based on factors such as renal function, age or patient/doctor preference for once- or twice-daily dosing regimens. Dose reduction of some NOACS should be considered in at-risk patient populations. PMID:27617088

  10. Contemporary anticoagulation therapy in patients undergoing percutaneous intervention.

    PubMed

    Bhatty, Shaun; Ali, Asghar; Shetty, Ranjith; Sumption, Kevin F; Topaz, On; Jovin, Ion S

    2014-04-01

    The proper use of anticoagulants is crucial for ensuring optimal patient outcomes post percutaneous interventions in the cardiac catheterization laboratory. Anticoagulant agents such as unfractionated heparin, a thrombin inhibitor; low-molecular weight heparins, predominantly Factor Xa inhibitors; fondaparinux, a Factor Xa inhibitor and bivalirudin, a direct thrombin inhibitor have been developed to target various steps in the coagulation cascade to prevent formation of thrombin. Optimal anticoagulation achieves the correct balance between thrombosis and bleeding and is related to optimal outcomes with minimal complications. This review will discuss the mechanisms and appropriate use of current and emerging anticoagulant therapies used during percutaneous interventions. PMID:24506409

  11. [Duration of anticoagulant therapy in venous thromboembolic complications].

    PubMed

    Kuznetsov, M R; Leontyev, S G; Neskhodimov, L A; Tolstikhin, V Yu; Khotinskiy, A A

    2016-01-01

    Adequate anticoagulant therapy is a general approach to treatment of deep vein thrombosis. However, the duration of anticoagulant therapy is not strictly specified in everyday clinical practice. The present article deals with various approaches to selecting the duration of therapy with anticoagulants based on the findings of studies, national and foreign clinical guidelines. The minimal duration of therapy for deep vein thrombosis and pulmonary thromboembolism amounts to 3 months in accordance with the national and American recommendations. For some cohorts of patients, continuation of therapy above 3 months is considered: patients with idiopathic thrombosis (the recommended duration of therapy of not less than 6 months), patients having persisting risk factor for relapse of thrombosis on termination of the main therapeutic course, oncological patients (6 month therapy followed by assessing the risk and benefit of continuing therapy with anticoagulants). Prolonged therapy of venous thromboembolism using unfractionated heparin or low-molecular-weight heparin followed by changing over to vitamin K antagonists is associated with decreased risk for thrombosis relapse approximately by 90%, however increasing the risk of haemorrhage. Currently, as an alternative, it is possible to consider administration of novel oral anticoagulants (rivaroxaban, dabigatran, apixaban) which beside high efficacy are associated with less risk of bleeding. The route of administration, no necessity to control the INR, and the minimal number of drug and food interactions make administration of new oral anticoagulants an attractive alternative to therapy with heparins and vitamin K antagonists. PMID:27100556

  12. [Progress of anticoagulation therapy in atrial fibrillation].

    PubMed

    Hernández Olmedo, Miguel; Suárez Fernández, Carmen

    2015-08-01

    Atrial fibrillation is currently a very prevalent disease and it represents one of the most common causes of disabling stroke. Antithrombotic therapies have reduced the incidence of this complication although they pose many limitations and difficulties. As a result, a large number of high risk patients do not receive an appropriate treatment. In recent years, four new oral anticoagulants (NOAC) with relevant advantages in comparison to vitaminK antagonists have been released. Four large phaseiii clinical trials have demonstrated that NOAC are at least as safe and efficacious as warfarin in stroke prevention in non-valve atrial fibrillation patients with moderate-high thrombotic risk, being their main advantage the reduction in intracranial hemorrhage. The arrival of these drugs has caused great expectations in the management of these patients but also new doubts. Lacking data in some subgroups of frail patients, the absence of specific antidotes available and specially their high cost represent nowadays the main limitations for their generalization. PMID:25192579

  13. Anti-coagulant therapy with dabigatran for cystic fibrosis patients.

    PubMed

    Bansal, Manvi; Ren, Clement L

    2016-08-01

    Patients with cystic fibrosis (CF) are at increased risk of venous thromboembolism, especially in association with central venous catheter use. Coumarin drugs and low molecular weight heparin are frequently used for anti-coagulant therapy, but are more challenging to administer in CF patients. Dabigatran, an oral thrombin antagonist, is an alternative anti-coagulant medication, but its use in CF has not been reported. We describe our experience in successfully using dabigatran for long-term anti-coagulation therapy in two CF patients. Our experience suggests that dabigatran can serve as an option for anticoagulation therapy in CF. Pediatr Pulmonol. 2016;51:E29-E30. © 2016 Wiley Periodicals, Inc. PMID:27128852

  14. Antithrombotic and Anticoagulant Therapy for Atrial Fibrillation.

    PubMed

    Dzeshka, Mikhail S; Lip, Gregory Y H

    2016-04-01

    As atrial fibrillation (AF) substantially increases the risk of stroke and other thromboembolic events, most AF patients require appropriate antithrombotic prophylaxis. Oral anticoagulation (OAC) with either dose-adjusted vitamin K antagonists (VKAs) (eg, warfarin) or non-VKA oral anticoagulants (eg, dabigatran, apixaban, rivaroxaban) can be used for this purpose unless contraindicated. Therefore, risk assessment of stroke and bleeding is an obligatory part of AF management, and risk has to be weighed individually. Antiplatelet drugs (eg, aspirin and clopidogrel) are inferior to OAC, both alone and in combination, with a comparable risk of bleeding events. PMID:26968670

  15. Personalized antiplatelet and anticoagulation therapy: applications and significance of pharmacogenomics.

    PubMed

    Beitelshees, Amber L; Voora, Deepak; Lewis, Joshua P

    2015-01-01

    In recent years, substantial effort has been made to better understand the influence of genetic factors on the efficacy and safety of numerous medications. These investigations suggest that the use of pharmacogenetic data to inform physician decision-making has great potential to enhance patient care by reducing on-treatment clinical events, adverse drug reactions, and health care-related costs. In fact, integration of such information into the clinical setting may be particularly applicable for antiplatelet and anticoagulation therapeutics, given the increasing body of evidence implicating genetic variation in variable drug response. In this review, we summarize currently available pharmacogenetic information for the most commonly used antiplatelet (ie, clopidogrel and aspirin) and anticoagulation (ie, warfarin) medications. Furthermore, we highlight the currently known role of genetic variability in response to next-generation antiplatelet (prasugrel and ticagrelor) and anticoagulant (dabigatran) agents. While compelling evidence suggests that genetic variants are important determinants of antiplatelet and anticoagulation therapy response, significant barriers to clinical implementation of pharmacogenetic testing exist and are described herein. In addition, we briefly discuss development of new diagnostic targets and therapeutic strategies as well as implications for enhanced patient care. In conclusion, pharmacogenetic testing can provide important information to assist clinicians with prescribing the most personalized and effective antiplatelet and anticoagulation therapy. However, several factors may limit its usefulness and should be considered. PMID:25897256

  16. Personalized antiplatelet and anticoagulation therapy: applications and significance of pharmacogenomics

    PubMed Central

    Beitelshees, Amber L; Voora, Deepak; Lewis, Joshua P

    2015-01-01

    In recent years, substantial effort has been made to better understand the influence of genetic factors on the efficacy and safety of numerous medications. These investigations suggest that the use of pharmacogenetic data to inform physician decision-making has great potential to enhance patient care by reducing on-treatment clinical events, adverse drug reactions, and health care-related costs. In fact, integration of such information into the clinical setting may be particularly applicable for antiplatelet and anticoagulation therapeutics, given the increasing body of evidence implicating genetic variation in variable drug response. In this review, we summarize currently available pharmacogenetic information for the most commonly used antiplatelet (ie, clopidogrel and aspirin) and anticoagulation (ie, warfarin) medications. Furthermore, we highlight the currently known role of genetic variability in response to next-generation antiplatelet (prasugrel and ticagrelor) and anticoagulant (dabigatran) agents. While compelling evidence suggests that genetic variants are important determinants of antiplatelet and anticoagulation therapy response, significant barriers to clinical implementation of pharmacogenetic testing exist and are described herein. In addition, we briefly discuss development of new diagnostic targets and therapeutic strategies as well as implications for enhanced patient care. In conclusion, pharmacogenetic testing can provide important information to assist clinicians with prescribing the most personalized and effective antiplatelet and anticoagulation therapy. However, several factors may limit its usefulness and should be considered. PMID:25897256

  17. Antiplatelet and anticoagulant therapy in elective percutaneous coronary intervention

    PubMed Central

    ten Berg, Jurriën M; Plokker, HW Thijs; Verheugt, Freek WA

    2001-01-01

    Thrombosis plays a major role in acute vessel closure both after coronary balloon angioplasty and after stenting. This review will address the role of antiplatelet and anticoagulant therapy in preventing early thrombotic complications after percutaneous coronary intervention. The focus will be on agents that are routinely available and commonly used. PMID:11806786

  18. [Serious surgical complications associated with chronic anticoagulant therapy].

    PubMed

    Pitrák, V; Hadacová, I; Hochová, I; Hoch, J

    2001-06-01

    Chronic anticoagulant treatment is administered mostly for cardiological reasons. Cumarin derivatires are used in the majority of cases (Warfarin, Pelentan). It is necessary to monitor this treatment regularly and to control the dose according to the INR value. Different complications can occur; the haemorrhage represents a serious one. The authors discuss several aspects of anticoagulant therapy and possible prevention of the complications. The importance of the problems is demonstrated on the authors' clinical experience--two cases of haemorrhage after Warfarin administration simulating an acute surgical event. PMID:11482149

  19. Application of the theory of planned behavior to oral anticoagulant therapy.

    PubMed

    Burns, Sharita

    2009-03-01

    Anticoagulation control is imperative for individuals who are prescribed long-term oral anticoagulation therapy. Therapeutic international normalized ratios decrease the risk of the thromboembolic complications that are associated with oral anticoagulation therapy. Individuals on oral anticoagulation therapy are often asked to make lifestyle modifications that can become barriers to medication adherence. The application of the theory of planned behavior to oral anticoagulation therapy can be used to assist advanced practice nurses in assessing individuals for the perceived barriers or obstacles that might interfere with the behavioral changes necessary to successfully comply with the recommended treatment plan. PMID:19298315

  20. Emerging anticoagulant therapies for atrial fibrillation: new options, new challenges.

    PubMed

    Mangiafico, R A; Mangiafico, M

    2012-01-01

    Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with an increased risk of stroke and systemic embolism. Oral anticoagulation with vitamin K antagonists (VKAs), such as warfarin, has historically been the mainstay of long-term thromboprophylaxis in AF patients. However, although highly effective, VKAs have a number of limitations that make their use difficult and cumbersome in clinical practice. They have a slow onset and offset of action, narrow therapeutic window, marked dose-response variability, and multiple food and drug interactions, and require frequent coagulation monitoring and dose adjustments. To overcome VKA drawbacks, several new oral anticoagulants have been recently developed for use in AF, and three of them, the direct thrombin inhibitor dabigatran etexilate and the direct factor Xa inhibitors rivaroxaban and apixaban, have completed phase III trials. New agents have proven to be noninferior or superior to warfarin for AF-related stroke prevention, with similar or better safety profiles. These new drugs, with their predictable anticoagulant effect that allows for fixed dosing with no need for coagulation monitoring, have the potential to greatly simplify anticoagulation therapy for AF. Dabigatran etexilate and rivaroxaban are already approved in the United States and Europe for stroke prevention in nonvalvular AF, and dabigatran etexilate has entered current AF guidelines as an alternative to warfarin. However, some issues with new compounds are still unresolved, such as the lack of antidotes and standardized tests to measure drug activity. Active postmarketing monitoring surveillance of effectiveness and safety is required in the implementation of new anticoagulant therapies. PMID:22830344

  1. Worldwide management of oral anticoagulant therapy: the ISAM study.

    PubMed

    Pengo, Vittorio; Pegoraro, Cinzia; Cucchini, Umberto; Iliceto, Sabino

    2006-02-01

    A multicenter, observational, retrospective, cross-sectional study of patients, receiving oral anticoagulation therapy (OAT) for stroke prophylaxis in chronic non-valvular atrial fibrillation (NVAF) was conducted in the US, Canada, France, Italy and Spain according to their predominant model of care [routine medical care (RMC) or Anticoagulation Clinic care (ACC)]. The study objectives were to assess anticoagulation control (time in target range), and to describe the features of the local model of care. Consecutive patients were recruited on the basis of a minimum of 60 days of oral anticoagulant treatment over a 12 month period, and clinic and physician details were captured by means of a structured face-to-face or telephone interview. Time in therapeutic range (TTR) was calculated by using linear interpolation between INR values. A total of 1511 patients were recruited, of whom 1445 were included in the analysis of TTR. TTR was higher in ACC (69.5% and 64.9% for Italy and Spain, respectively) with respect to RMC (58.1%, 62.8% and 59.3% for the US, Canada and France, respectively). Mean intervals between INR determinations were between 3 and 4 weeks. Dose changes in case of INR outside therapeutic range were more frequent in Spain and less frequent in France. Striking differences were observed in type of VKA used, specialists involved in patient management, and dosage instructions. Studying of anticoagulation management based on local models of care highlights important discrepancies among countries and suggests further standardization of the management of this important therapy is necessary. PMID:16475046

  2. The future prospects of pharmacogenetics in oral anticoagulation therapy.

    PubMed

    Kamali, Farhad; Pirmohamed, Munir

    2006-06-01

    Coumarins are the mainstay of oral anticoagulation for the treatment and prophylaxis of thromboembolic disorders. They have a narrow therapeutic index and regular monitoring is therefore required to avoid serious adverse effects. There is wide interindividual variability in dosage requirements, which makes anticoagulation response unpredictable. Current dosing titrations are haphazard and inconvenient and poor initial control leads to morbidity, and occasional mortality, because of bleeding and further thromboembolism. Recent discoveries have helped to characterize the factors that contribute to the interindividual variability in responses to coumarins. Patient and environmental factors that affect anticoagulation response to coumarins include age, body size, dietary vitamin K status, concurrent disease and drug interactions. More recently, single nucleotide polymorphisms in the 2C9 isoform of cytochrome P450 (CYP2C9) and vitamin K epoxide reductase (VKOR) have been shown to make significant contributions to the variability in coumarin dosage requirements. Polymorphisms in other genes that mediate the actions of coumarins may also contribute to this variability. Racial and cultural differences influence dosage requirements, which can be explained, at least in part, by genetic and dietary factors. Incorporation of genetic and environmental factors could help in the prediction of more individualized loading and maintenance doses for safer anticoagulation therapy. PMID:16722840

  3. Safety of anticoagulation in the elderly: reasons for discontinuing therapy.

    PubMed Central

    O'Neill, P. A.; Crossley, D.; Taberner, D. A.; Fairweather, D. S.

    1992-01-01

    We have conducted a retrospective study on the reasons for discontinuing anticoagulants in 50 patients over the age of 75 years compared with 198 adults under 75 years to determine the safety of therapy in the elderly. Venous thromboembolism and arterial embolization were the most common indications for therapy in the elderly and the median duration of therapy in all patients was 7 months (9 days-22 years). There were no deaths attributable to anticoagulants. There was no significant difference in the proportion of elderly patients who stopped treatment because of bleeding compared with 198 patients under 75 years (5/50 (10%) vs 12/198 (6.1%), P = 0.26), nor in the rate of bleeding between the two groups (5/52.5 (9.5%) treatment-years vs 12/249 (4.8%) treatment-years, P = 0.15). This complication rate does not suggest that age per se is a risk factor in the use of oral anticoagulants. PMID:1461856

  4. Pharmacogenomics of Anti-platelet and Anti-coagulation Therapy

    PubMed Central

    Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.

    2013-01-01

    Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323

  5. Considerations for long-term anticoagulant therapy in patients with venous thromboembolism in the novel oral anticoagulant era

    PubMed Central

    Toth, Peter P

    2016-01-01

    Background Patients who have had a venous thromboembolic event are generally advised to receive anticoagulant treatment for 3 months or longer to prevent a recurrent episode. Current guidelines recommend initial heparin and an oral vitamin K antagonist (VKA) for long-term anticoagulation. However, because of the well-described disadvantages of VKAs, including extensive food and drug interactions and the need for regular anticoagulation monitoring, novel oral anticoagulants (NOACs) have become an attractive option in recent years. These agents are given at fixed doses and do not require routine coagulation-time monitoring. The NOACs are discussed in this review with regard to the needs of patients on long-term anticoagulation. Methods Current guidelines from Europe and North America that refer to the treatment of deep vein thrombosis and/or pulmonary embolism are included, as well as published randomized Phase III clinical trials of NOACs. PubMed searches were used for sourcing case studies of long-term anticoagulant treatment, and results were filtered for human application and screened for relevance. Conclusion NOAC-based therapy showed a similar efficacy and safety profile to heparins/VKAs but without the need for regular anticoagulation monitoring or dietary adjustments, and can be taken as a fixed-dose regimen once or twice daily. This represents a significant step forward in facilitating the management of long-term anticoagulation therapy. Furthermore, in the EINSTEIN studies, improved patient satisfaction was documented with the NOAC rivaroxaban, which may result in better adherence to therapy and an overall reduction in the incidence of recurrent venous thromboembolism. PMID:26929637

  6. [Anticoagulant therapy in secondary prevention of coronary events].

    PubMed

    Bultas, Jan

    2014-12-01

    Secondary prevention of atherothrombotic events is the domain of antiplatelet therapy and according to present risk is used one drug strategy or combination of acetylsalicylic acid with ADP receptor blockers. The importance of the combination of dual antiplatelet therapy together with xabans or dabigatran was investigated in 6 clinical trials. Only one of them (ATLAS ACS 2-TIMI 51) indicated that treatment with small dose of rivaroxaban (2 × 2.5 mg) may be added to dual strategy of acetylsalicylic acid and clopidogrel. The risk of major bleeding event is increased and net clinical benefit is only about 0.5 % per year. Dual therapy with aspirin and prasugrel or tikagrelor is beneficial. In the second part of the review is discussed higher incidence of myocardial infarction in controlled group in the trial comparing treatment of dabigatran with warfarin. This relationship has not been resolved, however, in patients with higher risk of coronary events and indication of anticoagulant treatment with direct oral anticoagulants it is recommended to choose from xabans (apixaban and rivaroxaban). PMID:25692828

  7. Anticoagulant and Antiplatelet Therapy in Patients with Atrial Fibrillation and Coronary Artery Disease

    PubMed Central

    Mischke, Karl; Knackstedt, Christian; Marx, Nikolaus

    2012-01-01

    Anticoagulation represents the mainstay of therapy for most patients with atrial fibrillation. Patients on oral anticoagulation often require concomitant antiplatelet therapy, mostly because of coronary artery disease. After coronary stent implantation, dual antiplatelet therapy is necessary. However, the combination of oral anticoagulation and antiplatelet therapy increases the bleeding risk. Risk scores such as the CHA2DS2-Vasc score and the HAS-BLED score help to identify both bleeding and stroke risk in individual patients. The guidelines of the European Society of Cardiology provide a rather detailed recommendation for patients on oral anticoagulation after coronary stent implantation. However, robust evidence is lacking for some of the recommendations, and especially for new oral anticoagulants and new antiplatelets few or no data are available. This review addresses some of the critical points of the guidelines and discusses potential advantages of new anticoagulants in patients with atrial fibrillation after stent implantation. PMID:22577538

  8. Sex Differences in Patients Receiving Anticoagulant Therapy for Venous Thromboembolism

    PubMed Central

    Blanco-Molina, Angeles; Enea, Iolanda; Gadelha, Telma; Tufano, Antonella; Bura-Riviere, Alessandra; Di Micco, Pierpaolo; Bounameaux, Henri; González, José; Villalta, Jaume; Monreal, Manuel

    2014-01-01

    Abstract In patients with venous thromboembolism (VTE), the outcome during the course of anticoagulant therapy may differ according to the patient’s sex. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of VTE recurrences, major bleeding, and mortality due to these events according to sex. As of August 2013, 47,499 patients were enrolled in RIETE, of whom 24,280 (51%) were women. Women were older, more likely presented with pulmonary embolism (PE), and were more likely to have recent immobilization but less likely to have cancer than men. During the course of anticoagulation (mean duration: 253 d), 659 patients developed recurrent deep vein thrombosis (DVT), 576 recurrent PE, 1368 bled, and 4506 died. Compared with men, women had a lower rate of DVT recurrences (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.67–0.91), a similar rate of PE recurrences (HR: 0.98; 95% CI: 0.83–1.15), a higher rate of major bleeding (HR: 1.21; 95% CI: 1.09–1.35), and higher mortality due to PE (HR: 1.24; 95% CI: 1.04–1.47). On multivariable analysis, any influence of sex on the risk for recurrent DVT (HR: 0.88; 95% CI: 0.75–1.03), major bleeding (HR: 1.10; 95% CI: 0.98–1.24), or fatal PE (HR: 1.01; 95% CI: 0.84–1.22) was no longer statistically significant. In conclusion, women had fewer DVT recurrences and more bleeds than men during the course of anticoagulation. These differences were not due to sex, but very likely to other patient characteristics more common in female patients and differences in treatment choice. PMID:25398066

  9. Role of Antiplatelet Therapy and Anticoagulation in Nonischemic Cardiomyopathy.

    PubMed

    Carazo, Matthew; Berger, Jeffrey S; Reyentovich, Alex; Katz, Stuart D

    2016-01-01

    Heart failure continues to be a leading cause of morbidity and mortality throughout the United States. The pathophysiology of heart failure involves the activation of complex neurohormonal pathways, many of which mediate not only hypertrophy and fibrosis within ventricular myocardium and interstitium, but also activation of platelets and alteration of vascular endothelium. Platelet activation and vascular endothelial dysfunction may contribute to the observed increased risk of thromboembolic events in patients with chronic heart failure. However, current data from clinical trials do not support the routine use of chronic antiplatelet or oral anticoagulation therapy for ambulatory heart failure patients without other indications (atrial fibrillation and/or coronary artery disease) as the risk of bleeding seems to outweigh the potential benefit related to reduction in thromboembolic events. In this review, we consider the potential clinical utility of targeting specific pathophysiological mechanisms of platelet and vascular endothelial activation to guide clinical decision making in heart failure patients. PMID:26501990

  10. [Gastrointestinal bleeding associated with NSAIDs, antiplatelet therapy and anticoagulant agent].

    PubMed

    Lanas, Angel

    2012-09-01

    Following the trends observed for the last 2-3 years, the most significant and recent advances in the area of gastrointestinal lesions associated with anti-inflammatory drugs (NSAIDs) have focused on adverse effects in the distal intestine and on issues related to the toxicity associated with antiplatelet therapy. New data reinforce evidence that NSAIDs and antiplatelet therapy are associated with an increased risk of serious complications in both the upper and lower gastrointestinal tract, opening up several lines of research in prevention and therapy based on probiotics, antibiotics and mucosal protectants. The interaction between Helicobacter pylori infection and NSAIDs or aspirin remains controversial but a positive interaction between this bacterium and NSAIDs seems to be reinforced. Several systematic reviews confirm that the combination of gastrotoxic drugs significantly increases the risk of gastrointestinal bleeding, which should reinforce existing prevention strategies, and that new anticoagulant agents do not appear to reduce the risk of gastrointestinal bleeding. Once gastrointestinal hemorrhage has occurred, several studies have indicated the need to implement simpler prognostic scales than those used today. Notable innovations are the development of a disposable endoscope for acute upper gastrointestinal bleeding events and a promising new hemostatic technique, hemospray, applied locally over the bleeding lesion. PMID:23018006

  11. Anticoagulant therapy and its impact on dental patients: a review.

    PubMed

    Thean, D; Alberghini, M

    2016-06-01

    Several new oral anticoagulants have been studied in the past decade, and have now started to enter the market. These drugs are reported to be as effective as, or more effective than, warfarin. In Australia, the Therapeutic Goods Administration has approved dabigatran, rivaroxaban and apixaban. The use of these newer anticoagulants is likely to increase in time, and it is important for dentists to have a sound understanding of the mechanisms of action, reversal strategies, and management guidelines for patients taking oral anticoagulants. This article discusses the process of coagulation, available anticoagulants and their monitoring and reversal, and provides clinical advice on the management of patients on anticoagulants who require dental treatment. PMID:26042924

  12. Implant surgery and oral anticoagulant therapy: case report

    PubMed Central

    MIRANDA, M.; BOLLERO, P.; D’OVIDIO, N.; MARSANGO, V.; BARLATTANI, A.

    2014-01-01

    SUMMARY Objectives. This work aims to assess the risks both thromboembolic that bleeding of a management protocol “non-conservative” in patients on oral anticoagulant therapy (OAT) to be undergoing implant surgery. Materials and methods. We decided to take a surgical “non-conservative” protocol, to insert four implants in the aesthetic zone, without using flapless surgery and the surgical template. In accordance with the hematologist, the value of INR is lowered and warfarin was replaced with heparin low molecular weight, to have a better coagulation’s control. Results. The modern guidelines impose a protocol of conservative management in patients with OAT, with minimally invasive surgery, flapless, and use of surgical template to reduce the risk of uncontrolled bleeding. This, thanks to the team-work between dentist and hematologist, thanks to careful adjustment of INR and the use of local haemostatic agents, were not encountered any problems with bleeding or intra or postoperative. Conclusion. Surgical treatment of patients with OAT is a real problem for the oral surgeon, to treat every time in association with the hematologist. Applying this type of surgical procedure, different from today’s guidelines, in our experience there were no post-operative complications (bleeding or bleeding); osseointegration has not been compromised and the prosthetic rehabilitation was completed successfully. PMID:25694802

  13. Hemorrhagic complications of anticoagulant treatment: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

    PubMed

    Levine, Mark N; Raskob, Gary; Beyth, Rebecca J; Kearon, Clive; Schulman, Sam

    2004-09-01

    This chapter about hemorrhagic complications of anticoagulant treatment is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Bleeding is the major complication of anticoagulant therapy. The criteria for defining the severity of bleeding varies considerably between studies, accounting in part for the variation in the rates of bleeding reported. The major determinants of vitamin K antagonist-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that vitamin K antagonist therapy, targeted international normalized ratio (INR) of 2.5 (range, 2.0 to 3.0), is associated with a lower risk of bleeding than therapy targeted at an INR > 3.0. The risk of bleeding associated with IV unfractionated heparin (UFH) in patients with acute venous thromboembolism (VTE) is < 3% in recent trials. This bleeding risk may increase with increasing heparin dosages and age (> 70 years). Low molecular weight heparin (LMWH) is associated with less major bleeding compared with UFH in acute VTE. UFH and LMWH are not associated with an increase in major bleeding in ischemic coronary syndromes, but are associated with an increase in major bleeding in ischemic stroke. Information on bleeding associated with the newer generation of antithrombotic agents has begun to emerge. In terms of treatment decision making for anticoagulant therapy, bleeding risk cannot be considered alone, ie, the potential decrease in thromboembolism must be balanced against the potential increased bleeding risk. PMID:15383476

  14. Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy.

    PubMed

    Maas, Angela H E M; Euler, Mia von; Bongers, Marlies Y; Rolden, Herbert J A; Grutters, Janneke P C; Ulrich, Lian; Schenck-Gustafsson, Karin

    2015-12-01

    A growing number of premenopausal women are currently using antithrombotic and/or (dual) antiplatelet therapy for various cardiovascular indications. These may induce or exacerbate abnormal uterine bleeding and more awareness and knowledge among prescribers is required. Heavy and irregular menstrual bleeding is common in women in their forties and may have a variety of underlying causes that require different treatment options. Thus using anticoagulants in premenopausal women demands specific expertise and close collaboration between cardiovascular physicians and gynecologists. In this article we summarize the scope of the problem and provide practical recommendations for the care for young women taking anticoagulants and/or (dual) antiplatelet therapy. We also recommend that more safety data on uterine bleeding with novel anticoagulants in premenopausal women should be obtained. PMID:26358933

  15. Hemorrhagic cholecystitis as a complication of anticoagulant therapy: role of CT in its diagnosis.

    PubMed

    Pandya, Rajul; O'Malley, Charles

    2008-01-01

    Hemorrhage within the gallbladder lumen is a rare but potentially fatal complication of acute cholecystitis. Concomitant anticoagulant therapy increases the chances of hemorrhage. In this case report we describe one such case which showed active extravasation of the contrast into the lumen of the gallbladder. Early diagnosis of this potentially fatal condition is important to facilitate urgent surgical treatment. PMID:18629579

  16. How I treat patients with inherited bleeding disorders who need anticoagulant therapy.

    PubMed

    Martin, Karlyn; Key, Nigel S

    2016-07-14

    Situations that ordinarily necessitate consideration of anticoagulation, such as arterial and venous thrombotic events and prevention of stroke in atrial fibrillation, become challenging in patients with inherited bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease. There are no evidence-based guidelines to direct therapy in these patients, and management strategies that incorporate anticoagulation must weigh a treatment that carries a risk of hemorrhage in a patient who is already at heightened risk against the potential consequences of not treating the thrombotic event. In this paper, we review atherothrombotic disease, venous thrombotic disease, and atrial fibrillation in patients with inherited bleeding disorders, and discuss strategies for using anticoagulants in this population using cases to illustrate these considerations. PMID:27106121

  17. How I treat patients with inherited bleeding disorders who need anticoagulant therapy

    PubMed Central

    Martin, Karlyn

    2016-01-01

    Situations that ordinarily necessitate consideration of anticoagulation, such as arterial and venous thrombotic events and prevention of stroke in atrial fibrillation, become challenging in patients with inherited bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease. There are no evidence-based guidelines to direct therapy in these patients, and management strategies that incorporate anticoagulation must weigh a treatment that carries a risk of hemorrhage in a patient who is already at heightened risk against the potential consequences of not treating the thrombotic event. In this paper, we review atherothrombotic disease, venous thrombotic disease, and atrial fibrillation in patients with inherited bleeding disorders, and discuss strategies for using anticoagulants in this population using cases to illustrate these considerations. PMID:27106121

  18. [Quality of life of patients with venous thromboses in different variants of anticoagulant therapy].

    PubMed

    Kalinin, R E; Suchkov, I A; Pshennikov, A S; Agapov, A B

    2016-01-01

    The CIVIQ questionnaire was used to evaluate quality of life of patients presenting with deep vein thrombosis of lower limbs in different variants of anticoagulant therapy. The study included a total of 170 patients who were depending on the variant of anticoagulant therapy subdivided into 3 groups: Group One (comprising 48 patients) taking rivaroxaban as monotherapy; Group Two (consisting of 73 subjects) receiving low molecular weight heparin (enoxaparin sodium) followed by adjusting the warfarin dose, and Group Three (including 49 patients) receiving low molecular weight heparin (enoxaparin sodium) followed by rivaroxaban. The total value of the level of quality of life in all groups showed a tendency towards restoration. However, patients taking warfarin during the follow-up period were found to have negative dynamics by the 6th month of treatment. It was revealed that quality of life on all parameters was higher in patients taking rivaroxaban and lower in those taking warfarin. The parameters of the physical component of health turned out to depend upon the degree of recanalization of the thrombus. After 6 months of anticoagulant therapy patients taking rivaroxaban (Groups One and Three) were found to have good recanalization in 87.5 and 87.7% of cases, respectively, while in Group Two being observed in 54.8% of patients only. Taking an anticoagulant at a fixed dose not requiring laboratory control (rivaroxaban) increases patient compliance, thus leading to improvement of both mental and social wellbeing. PMID:27336328

  19. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use

    PubMed Central

    Lensing, Anthonie W. A.; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A.; Cohen, Alexander T.; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S.; Prins, Martin H.

    2016-01-01

    Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an “unacceptable health risk” during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration. PMID:26696010

  20. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use.

    PubMed

    Martinelli, Ida; Lensing, Anthonie W A; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S; Prins, Martin H

    2016-03-17

    Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an "unacceptable health risk" during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration. PMID:26696010

  1. Andexanet: Effectively Reversing Anticoagulation.

    PubMed

    Lippi, Giuseppe; Sanchis-Gomar, Fabian; Favaloro, Emmanuel J

    2016-06-01

    Despite direct oral anticoagulants becoming a mainstay of anticoagulant therapy, the effective, timely, and safe reversal of their anticoagulant effect remains challenging. Emerging evidence attests that andexanet, a recombinant and inactive variant of native factor X (FXa), competitively inhibits and counteracts the anticoagulant effect of many inhibitors of native activated FXa. PMID:27048885

  2. Intracerebral hemorrhage during treatment with oral anticoagulants. Risk factors, therapy and prognosis.

    PubMed

    Ernestus, R I; Speder, B; Pakos, P; Hildebrandt, G; Klug, N

    1994-01-01

    Intracerebral hemorrhage (ICH) during oral anticoagulation is a serious complication, which is mostly fatal for the multimorbid patient. In the present retrospective study of 53 patients with ICH during treatment with a cumarin derivative (Phenoprocoumon, Marcumar), we investigated the relationship between therapy and preexisting parameters such as age, location, level of consciousness, additional bleeding risks, and the degree of anticoagulation, which were assumed to be of prognostic relevance. The therapeutic management of ICH during treatment with anticoagulants was determined predominantly by location of the hematoma, patient's age, and additional bleeding risks, but less by level of consciousness and initial thromboplastin time (Quick's test). As a consequence of the individual analysis of these 5 parameters, age over 60 years, location of hematoma in the midline or ventricles, coma, additional bleeding risks such as arterial hypertension and trauma, and Quick's test below 15% at the time of bleeding were supposed to be responsible for poor prognosis. Mortality increased with a rising number of poor prognostic factors, independently of surgical or conservative treatment. In consequence, prognosis of ICH during oral anticoagulation is predominantly influenced by the number of such disadvantageous indicators and only little by therapy. PMID:8053274

  3. Curative effect of mechanical heart valve replacement and anticoagulant therapy after surgery.

    PubMed

    Chuai, J B; Shi, L; Ma, X Y; Wu, D; Kang, K; Jiang, S L

    2016-01-01

    This study was carried out to determine the curative effect of low-intensity anticoagulant therapy by observing the oral administration of warfarin (anticoagulant therapy) on patients who had undergone mechanical heart valve replacement (MHVR) surgery with subsequent anticoagulation complications. Fifty patients who underwent MHVR in the Second Affiliated Hospital of Harbin Medical University and 52 patients in the Cardiovascular Surgery of Daqing Oilfield General Hospital between January 2013 and January 2016 were selected (63 males and 39 females, ages 26-77 years). They took warfarin after treatment and were followed-up by means of outpatient review and telephone after leaving the hospital. The effect of warfarin and the occurrence of anticoagulation complications were analyzed. The operations lasted 230±106 min, extracorporeal circulation for 110±50 min and aorta occlusion for 82±23 min. During post-operation 3 patients developed skin purpura and one patient died. During follow-up we found 3 cases of anemia caused by excessive menstruation, 4 cases of hematuresis, 3 cases of peated epistaxis, 1 case of gastrointestinal bleeding, 1 case of cerebral hemorrhage, 1 case of embolism in the lower limbs and 1 case of cerebral infarction, although they all improved or were totally cured. Therefore, the incidence of complications can be reduced significantly by the correct administration of warfarin as well as timely monitoring of interference factors after MHVR. PMID:27049085

  4. Fatal Events in Cancer Patients Receiving Anticoagulant Therapy for Venous Thromboembolism

    PubMed Central

    Farge, Dominique; Trujillo-Santos, Javier; Debourdeau, Philippe; Bura-Riviere, Alessandra; Rodriguez-Beltrán, Eva Maria; Nieto, Jose Antonio; Peris, Maria Luisa; Zeltser, David; Mazzolai, Lucia; Hij, Adrian; Monreal, Manuel

    2015-01-01

    Abstract In cancer patients treated for venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), analyzing mortality associated with recurrent VTE or major bleeding is needed to determine the optimal duration of anticoagulation. This was a cohort study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry database to compare rates of fatal recurrent PE and fatal bleeding in cancer patients receiving anticoagulation for VTE. As of January 2013, 44,794 patients were enrolled in RIETE, of whom 7911 (18%) had active cancer. During the course of anticoagulant therapy (mean, 181 ± 210 days), 178 cancer patients (4.3%) developed recurrent PE (5.5 per 100 patient-years; 95% CI: 4.8–6.4), 194 (4.7%) had recurrent DVT (6.2 per 100 patient-years; 95% confidence interval [CI]: 5.3–7.1), and 367 (8.9%) bled (11.3 per 100 patient-years; 95% CI: 10.2–12.5). Of 4125 patients initially presenting with PE, 43 (1.0%) died of recurrent PE and 45 (1.1%) of bleeding; of 3786 patients with DVT, 19 (0.5%) died of PE, and 55 (1.3%) of bleeding. During the first 3 months of anticoagulation, there were 59 (1.4%) fatal PE recurrences and 77 (1.9%) fatal bleeds. Beyond the third month, there were 3 fatal PE recurrences and 23 fatal bleeds. In RIETE cancer patients, the rate of fatal recurrent PE or fatal bleeding was much higher within the first 3 months of anticoagulation therapy. PMID:26266353

  5. The New Oral Anticoagulants for the Treatment of Venous Thromboembolism: A New Paradigm Shift in Antithrombotic Therapy

    PubMed Central

    Galanis, Taki; Keiffer, Gina; Merli, Geno

    2014-01-01

    Background Several novel oral anticoagulants have been studied for the prevention and treatment of venous thromboembolism (VTE) in different patient populations. Clinicians will increasingly encounter scenarios in which they must choose among these and conventional anticoagulants for the treatment of this potentially fatal condition. Objective To review the results of Phase III clinical trials that investigated the novel oral anticoagulants for the treatment of deep vein thrombosis and pulmonary embolism. Potential advantages and disadvantages of these anticoagulant agents with respect to each other and conventional therapy will also be explored through a case-based approach. Methods A literature search in PubMed was conducted that identified Phase III clinical trials investigating the novel oral anticoagulant agents for the treatment of VTE. Results The new oral anticoagulant agents have been shown to be as safe and effective for the treatment of VTE as conventional therapies. Conclusions These novel, oral anticoagulant agents are legitimate options for the treatment of VTE. A careful assessment of a patient׳s comorbidities, medication use, and laboratory results should be undertaken before prescribing the new oral anticoagulant agents for patients with VTE. PMID:25352938

  6. Preferences for anticoagulation therapy in atrial fibrillation: the patients' view.

    PubMed

    Böttger, Björn; Thate-Waschke, Inga-Marion; Bauersachs, Rupert; Kohlmann, Thomas; Wilke, Thomas

    2015-11-01

    Since the introduction of new oral anticoagulants (NOACs), besides vitamin-K antagonists, an additional option for stroke prevention of patients with atrial fibrillation (AF) is available. The objective of this study was to assess AF patients' preferences with regard to the attributes of these different treatment options. We conducted a multicenter study among randomly selected physicians. Preferences were assessed by computer-assisted telephone interviews. We used a discrete-choice-experiment (DCE) with four convenience-related treatment dependent attributes (need of bridging: yes/no, interactions with food/nutrition: yes/no, need of INR controls/dose adjustment: yes/no; frequency of intake: once/twice daily) and one comparator attribute (distance to practitioner: <1 km/>15 km). Preferences measured in the interviews were analyzed descriptively and based on a conditional logit regression model. A total of 486 AF patients (age: 73.9 ± 8.2 years; 43.2 % female; mean CHA2DS2-VASc: 3.7 ± 1.6; current medication: 48.1 % rivaroxaban, 51.9 % VKA) could be interviewed. Regardless of type of medication, patients significantly preferred the attribute levels (in order of patients' importance) "once daily intake" (Level: once = 1 vs. twice = 0; Coefficient = 0.615; p < 0.001), "bridging necessary" (yes = 1 vs. no = 0; -0.558; p < 0.001), "distance to practitioner of ≤1 km (>15 km = 0 vs. ≤1 km = 1; 0.494; p < 0.001), "interactions with food/nutrition" (yes = 1 vs. no = 0; -0.332; p < 0.001) and "need of INR controls/dose adjustment" (yes = 1 vs. no = 0; -0.127; p < 0.001). In our analyses, "once daily frequency of intake" was the most important OAC-attribute for patients' choice followed by "no bridging necessary" and "no interactions with food/nutrition". Thus, patients with AF seem to prefer treatment options which are easier to administer. PMID:26260625

  7. Quality of anticoagulation therapy in neurological patients in a tertiary care hospital in north India

    PubMed Central

    Singh, Prabhat; Kalita, J.; Misra, U.K.

    2016-01-01

    Background & objectives: There is paucity of studies on the quality of anticoagulation in neurological patients from India. This study evaluates the quality of oral anticoagulation therapy in neurology patients. Methods: Consecutive patients attending a tertiary care neurology service in north India who were prescribed oral anticoagulant (OAC), were included. Their international normalized ratio (INR) values were prospectively monitored and the earlier INR values of the patients who were already on OAC were retrospectively analyzed. The patients with multi-organ dysfunction, pregnancy and those below 18 yr of age were excluded. The therapeutic INR range was defined as per standard recommendations. The level of anticoagulation, factors interfering with OAC and complications were noted. Results: The results were based on 77 patients with median age 40 yr. Fifty one patients received OAC for secondary stroke prevention, 23 for cerebral venous sinus thrombosis (CVST) and three for deep vein thrombosis (DVT). A total 167.9 person-years of follow up was done with a median of 1.2 (0.3-9.3) years. Of the 1287 INR reports, 505 (39.3%) reports were in the therapeutic range, 496 (38.5%) were below and 282 (21.91%) were above the therapeutic level. Stable INR was obtained in 33 (42.86%) patients only. INR level was improved by dose adjustment in 20 (26%), drug modification in two (2.6%), and dietary adjustment in six (7.8%) patients. Three patients were sensitive and five were resistant to OAC. Complications were noted in 28 instances; thromboembolic in 16 and haemorrhagic stroke in 12. The overall complication rate was 16.7 per 100 person-years. Interpretation & conclusions: It may be concluded that stable therapeutic INR is difficult to maintain in neurological patients. Optimal modification of diet, drug and dose of oral anticoagulant may help in stabilization of INR. PMID:27377498

  8. Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials.

    PubMed Central

    Collins, R.; MacMahon, S.; Flather, M.; Baigent, C.; Remvig, L.; Mortensen, S.; Appleby, P.; Godwin, J.; Yusuf, S.; Peto, R.

    1996-01-01

    OBJECTIVES: Most randomised trials of anticoagulant therapy for suspected acute myocardial infarction have been small and, in some, aspirin and fibrinolytic therapy were not used routinely. A systematic overview (meta-analysis) of their results is needed, in particular to assess the clinical effects of adding heparin to aspirin. DESIGN: Computer aided searches, scrutiny of reference lists, and inquiry of investigators and companies were used to identify potentially eligible studies. On central review, 26 studies were found to involve unconfounded randomised comparisons of anticoagulant therapy versus control in suspected acute myocardial infarction. Additional information on study design and outcome was sought by correspondence with study investigators. SUBJECTS: Patients with suspected acute myocardial infarction. INTERVENTIONS: No routine aspirin was used among about 5000 patients in 21 trials (including half of one small trial) that assessed heparin alone or heparin plus oral anticoagulants, and aspirin was used routinely among 68,000 patients in six trials (including the other half of one small trial) that assessed the addition of intravenous or high dose subcutaneous heparin. MAIN OUTCOME MEASUREMENTS: Death, reinfarction, stroke, pulmonary embolism, and major bleeds (average follow up of about 10 days). RESULTS: In the absence of aspirin, anticoagulant therapy reduced mortality by 25% (SD 8%; 95% confidence interval 10% to 38%; 2P = 0.002), representing 35 (11) fewer deaths per 1000. There were also 10 (4) fewer strokes per 1000 (2P = 0.01), 19 (5) fewer pulmonary emboli per 1000 (2P < 0.001), and non-significantly fewer reinfarctions, with about 13 (5) extra major bleeds per 1000 (2P = 0.01). Similar sized effects were seen with the different anticoagulant regimens studied. In the presence of aspirin, however, heparin reduced mortality by only 6% (SD 3%; 0% to 10%; 2P = 0.03), representing just 5 (2) fewer deaths per 1000. There were 3 (1.3) fewer

  9. Long-Term Anticoagulant Therapy of Patients with Venous Thromboembolism. What Are the Practices?

    PubMed

    Mahé, Isabelle; Sterpu, Raluca; Bertoletti, Laurent; López-Jiménez, Luciano; Mellado Joan, Meritxell; Trujillo-Santos, Javier; Ballaz, Aitor; Hernández Blasco, Luis Manuel; Marchena, Pablo Javier; Monreal, Manuel

    2015-01-01

    Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26-3.23), age >70 years (OR 1.15, 95% CI 1.06-1.24), immobility (OR 2.06, 95% CI 1.93-2.19), renal insufficiency (OR 2.42, 95% CI 2.15-2.71) and anemia (OR 1.75, 95% CI 1.65-1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64-2.06), immobility (OR 1.51, 95% CI 1.30-1.76) and metastases (OR 3.22, 95% CI 2.87-3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision. PMID:26076483

  10. Long-Term Anticoagulant Therapy of Patients with Venous Thromboembolism. What Are the Practices?

    PubMed Central

    Mahé, Isabelle; Sterpu, Raluca; Bertoletti, Laurent; López-Jiménez, Luciano; Mellado Joan, Meritxell; Trujillo-Santos, Javier; Ballaz, Aitor; Hernández Blasco, Luis Manuel; Marchena, Pablo Javier; Monreal, Manuel

    2015-01-01

    Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26–3.23), age >70 years (OR 1.15, 95% CI 1.06–1.24), immobility (OR 2.06, 95% CI 1.93–2.19), renal insufficiency (OR 2.42, 95% CI 2.15–2.71) and anemia (OR 1.75, 95% CI 1.65–1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64–2.06), immobility (OR 1.51, 95% CI 1.30–1.76) and metastases (OR 3.22, 95% CI 2.87–3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision. PMID:26076483

  11. Clinical Outcomes of Anticoagulation Therapy in Patients With Symptomatic Spontaneous Isolated Dissection of the Superior Mesenteric Artery

    PubMed Central

    Han, Youngjin; Cho, Yong-Pil; Ko, Gi-Young; Seo, Dong Wan; Kim, Min-Ju; Kwon, Hyunwook; Kim, Hyangkyoung; Kwon, Tae-Won

    2016-01-01

    Abstract The aim of this study was to determine the clinical outcomes of long-term anticoagulation therapy in patients with symptomatic spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) and to evaluate whether conservative treatment with anticoagulation therapy is a safe and effective treatment modality for these patients. In this single center, observational cohort study, data from a prospectively recruiting symptomatic SIDSMA registry, including demographics, risk factors of interest, clinical characteristics and outcomes, and initial and follow-up computed tomography angiography (CTA) findings, were analyzed retrospectively. During an 8-year period, a total of 52 consecutive patients who underwent conservative treatment with the use of long-term anticoagulation were included in this study. Clinical symptoms resolved within 11 days in all except 4 patients (7.7%); 3 received endovascular treatment for persistent symptoms and 1 received surgical repair. The mean duration of anticoagulation therapy was 9 (range: 3–60) months. A follow-up CTA showed complete remodeling in 20 (41.7%) patients, and the mean diameter and the incidence of false lumen thrombosis were also decreased significantly. There was no anticoagulation therapy-related mortality or morbidity except 2 (4.2%) minor bleeding complications, and no symptomatic recurrence or aggravation of the dissection occurred during the mean follow-up period of 47.5 (range: 10–97) months. The present study showed that long-term anticoagulation therapy could result in a high rate of complete remodeling during the natural course of symptomatic SIDSMA. Conservative treatment with long-term anticoagulation therapy could be an optimal treatment strategy for symptomatic SIDSMA. PMID:27100453

  12. Clinical Outcomes of Anticoagulation Therapy in Patients With Symptomatic Spontaneous Isolated Dissection of the Superior Mesenteric Artery.

    PubMed

    Han, Youngjin; Cho, Yong-Pil; Ko, Gi-Young; Seo, Dong Wan; Kim, Min-Ju; Kwon, Hyunwook; Kim, Hyangkyoung; Kwon, Tae-Won

    2016-04-01

    The aim of this study was to determine the clinical outcomes of long-term anticoagulation therapy in patients with symptomatic spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) and to evaluate whether conservative treatment with anticoagulation therapy is a safe and effective treatment modality for these patients.In this single center, observational cohort study, data from a prospectively recruiting symptomatic SIDSMA registry, including demographics, risk factors of interest, clinical characteristics and outcomes, and initial and follow-up computed tomography angiography (CTA) findings, were analyzed retrospectively.During an 8-year period, a total of 52 consecutive patients who underwent conservative treatment with the use of long-term anticoagulation were included in this study. Clinical symptoms resolved within 11 days in all except 4 patients (7.7%); 3 received endovascular treatment for persistent symptoms and 1 received surgical repair. The mean duration of anticoagulation therapy was 9 (range: 3-60) months. A follow-up CTA showed complete remodeling in 20 (41.7%) patients, and the mean diameter and the incidence of false lumen thrombosis were also decreased significantly. There was no anticoagulation therapy-related mortality or morbidity except 2 (4.2%) minor bleeding complications, and no symptomatic recurrence or aggravation of the dissection occurred during the mean follow-up period of 47.5 (range: 10-97) months.The present study showed that long-term anticoagulation therapy could result in a high rate of complete remodeling during the natural course of symptomatic SIDSMA. Conservative treatment with long-term anticoagulation therapy could be an optimal treatment strategy for symptomatic SIDSMA. PMID:27100453

  13. [Perioperative Management of Lung Cancer Patients with atrial fibrillation being treated by antiplatelet or anticoagulant therapy].

    PubMed

    Ishikawa, Shinya; Kasai, Yoshitaka; Matsuura, Natsumi; Tarumi, Shintaro; Nakano, Jun; Okuda, Masaya; Goto, Masashi; Ryu, Dagu; Go, Tetsuhiko; Yokomise, Hiroyasu

    2015-04-01

    In an aging society, the high incidence of surgery for the patients with ischemic heart disease(IHD)or atrial fibrillation(Af) under antiplatelet or anticoagulant therapy is a great problem. Interruption of antiplatelet or anticoagulant oral agents in the perioperative period may increase the risk of coronary or cerebral events. We retrospectively reviewed the surgical outcomes for lung cancer patients with IHD or Af. We reviewed 135 patients with lung cancer(41~88 years;97 men) who had preoperative oral administration of antiplatelet or anticoagulant drugs for IHD or Af between 2005 and 2012 at 2 centers, and analyzed retrospectively the perioperative medications and complications. IHD, Af and vasospastic angina(VSA) were complicated in 94, 33 and 8 patients, respectively. Drugeluted and bare-metal stents had been placed in 18 and 19 patients. Oral agents were aspirin in 68 patients, ticlopidine in 10 patients, clopidogrel in 15 patients and warfarin in 25 patients. These agents were stopped 2 to 60 days before surgery. Perioperative heparinization was performed in 22 patients. Oral agents were restarted after confirmation of hemostasis and no need for further invasive treatment. The surgical procedures were lobectomy in 88 patients, segmentectomy in 19 and partial resection in 25. There were no hemorrhagic or thromboembolic complications in a perioperative period except 1 case of pulmonary hemorrhage and 1 case of cerebral infarction. No perioperative hospital death was documented. Short-term interruption of antiplatelet or anticoagulant drugs before lung cancer surgery and heparinization was acceptable from the view of perioperative outcomes. PMID:25836998

  14. Safety assessment of anticoagulation therapy in patients with hemorrhagic cerebral venous thrombosis

    PubMed Central

    Riasi, Hamid Reza; Noureddine, Ali; Masoudinezhad, Shahram; Yazdani, Siamak; Mirzae, Mohammad Mousavi; Razavi, Atena Sharifi; Ghandehari, Kosar

    2013-01-01

    Background Anticoagulation therapy is a routine treatment in patients with hemorrhagic cerebral venous thrombosis (CVT). However, fear of hemorrhagic complications and deterioration course following anticoagulation often disturbs the responsible physician. Methods This was a Prospective observational study on consecutive CVT patients with hemorrhagic venous infarction or subarachnoid hemorrhage (SAH) admitted in Ghaem Hospital, Mashhad, Iran, during 2006-2012. The diagnosis of CVT in suspected cases was confirmed by magnetic resonance imaging/magnetic resonance venography (MRI/MRV), and computerized tomography (CT) angiography following established diagnostic criteria. Demographic data, clinical manifestations from onset to end of the observation period, location of thrombus, location and size of infarction and hemorrhage, and clinical course during treatment were recorded. Choice of the treatment was left to the opinion of the treating physician. Clinical course during 1 week of treatment was assessed based on the baseline modified National Institute of Health Stroke Scale (NIHSS) score. Three or more points decrease or increase of modified NIHSS after 1 week of treatment was considered as improvement or deterioration courses, respectively. Other clinical courses were categorized as stabilization course. Results 102 hemorrhagic CVT patients (80 females, 22 males) with mean age of 38.6 ± 8 years were prospectively investigated. Of the 102 hemorrhagic CVT patients in the acute phase, 52 patients (50.9%) were anticoagulated with adjusted dose intravenous heparin infusion and 50 cases (49.1%) received subcutaneous enoxaparin 1mg/Kg twice daily. Decreased consciousness had a significant effect on the clinical course of the patients (X2 = 9.493, df = 2, P = 0.009). Presence of SAH had no significant effect on the clinical course of our anticoagulated hemorrhagic CVT cases (X2 = 0.304, df = 2, P = 0.914). Extension of Infarction in more than two thirds of a hemisphere

  15. Characteristics of Symptomatic Intracranial Hemorrhage in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulant Therapy

    PubMed Central

    2015-01-01

    Objectives The first non-vitamin K antagonist oral anticoagulant (NOAC) introduced to the market in Japan was dabigatran in March 2011, and three more NOACs, rivaroxaban, apixaban, and edoxaban, have since become available. Randomized controlled trials of NOACs have revealed that intracranial hemorrhage (ICH) occurs less frequently with NOACs compared with warfarin. However, the absolute incidence of ICH associated with NOACs has increased with greater use of these anticoagulants, and we wanted to explore the incidence, clinical characteristics, and treatment course of patients with NOACs-associated ICH. Methods We retrospectively analyzed the characteristics of symptomatic ICH patients receiving NOACs between March 2011 and September 2014. Results ICH occurred in 6 patients (5 men, 1 woman; mean ± SD age, 72.8 ± 3.2 years). Mean time to onset was 146.2 ± 111.5 days after starting NOACs. Five patients received rivaroxaban and 1 patient received apixaban. None received dabigatran or edoxaban. Notably, no hematoma expansion was observed within 24 h of onset in the absence of infusion of fresh frozen plasma, activated prothrombin complex concentrate, recombinant activated factor VIIa or hemodialysis. When NOAC therapy was initiated, mean HAS-BLED and PANWARDS scores were 1.5 ± 0.5 and 39.5 ± 7.7, respectively. Mean systolic blood pressure was 137.8 ± 15.9 mmHg within 1 month before spontaneous ICH onset. Conclusion Six symptomatic ICHs occurred early in NOAC therapy but hematoma volume was small and did not expand in the absence of infusion of reversal agents or hemodialysis. The occurrence of ICH during NOAC therapy is possible even when there is acceptable mean systolic blood pressure control (137.8 ± 15.9 mmHg) and HAS-BLED score ≤ 2. Even stricter blood pressure lowering and control within the acceptable range may be advisable to prevent ICH during NOAC therapy. PMID:26171862

  16. Discontinuation of Anticoagulant or Antiplatelet Therapy for Transrectal Ultrasound-Guided Prostate Biopsies: A Single-Center Experience

    PubMed Central

    Casey, Rowan G; Galvin, David J; Manecksha, Rustom P; Varadaraj, Haradikar; McDermott, TED; Grainger, Ronald; Lynch, Thomas H

    2012-01-01

    Purpose Historically, it was thought that hemorrhagic complications were increased with transrectal ultrasound-guided prostate biopsies (TRUS biopsy) of patients receiving anticoagulation/antiplatelet therapy. However, the current literature supports the continuation of anticoagulation/antiplatelet therapy without additional morbidity. We assessed our experience regarding the continuation of anticoagulation/antiplatelet therapy during TRUS biopsy. Materials and Methods A total of 91 and 98 patients were included in the anticoagulation/antiplatelet (group I) and control (group II) groups, respectively. Group I subgroups consisted of patients on monotherapy or dual therapy of aspirin, warfarin, clopidogrel, or low molecular weight heparin. The TRUS biopsy technique was standardized to 12 cores from the peripheral zones. Patients completed a questionnaire over the 7 days following TRUS biopsy. The questionnaire was designed to assess the presence of hematuria, rectal bleeding, and hematospermia. Development of rectal pain, fever, and emergency hospital admissions following TRUS biopsy were also recorded. Results The patients' mean age was 65 years (range, 52 to 74 years) and 63.5 years (range, 54 to 74 years) in groups I and II, respectively. The overall incidence of hematuria was 46% in group I compared with 63% in group II (p=0.018). The incidence of hematospermia was 6% and 10% in groups I and II, respectively. The incidence of rectal bleeding was similar in group I (40%) and group II (39%). Statistical analysis was conducted by using Fisher exact test. Conclusions There were fewer hematuria episodes in anticoagulation/antiplatelet patients. This study suggests that it is not necessary to discontinue anticoagulation/antiplatelet treatment before TRUS biopsy. PMID:22536465

  17. Safety of IVF under anticoagulant therapy in patients at risk for thrombo-embolic events.

    PubMed

    Yinon, Yoav; Pauzner, Rachel; Dulitzky, Mordechai; Elizur, Shai E; Dor, Jehoshua; Shulman, Adrian

    2006-03-01

    The objective of this study was to assess the safety of induction of ovulation and oocyte retrieval in patients at risk of thrombosis, necessitating treatment with anticoagulants. Twenty-four patients considered as high risk for a thromboembolic event underwent 73 IVF cycles and 68 oocyte retrieval procedures, and were treated concomitantly with anticoagulation therapy (low molecular weight heparin; LMWH). A subgroup of five patients considered at especially high risk for thrombosis was isolated. These patients were prepared for oocyte retrieval using a controlled spontaneous cycle. All these patients were programmed exclusively for surrogacy. Nineteen women underwent 49 cycles of ovulation induction with gonadotrophins. The average peak oestradiol concentration was 1791 +/- 1420 pg/ml with an average of 13.5 +/- 8.4 oocytes retrieved in each cycle. The five patients from the very high risk group underwent 24 cycles: the average peak oestradiol concentration was 163 +/- 98 pg/ml. In 18, an egg was retrieved and in 14, fertilization was achieved. No bleeding or thromboembolic complications were noted during treatment of both groups of patients. It is concluded that during induction of ovulation in patients at risk for thrombosis, the introduction of LMWH as a cycle protective treatment was not associated with any medical complication. The use of a controlled spontaneous cycle with LMWH is suggested in very high risk patients. PMID:16578908

  18. Optimizing adjunctive antithrombotic and anticoagulant therapy in primary PCI for STEMI.

    PubMed

    Deharo, Pierre; Rahbi, Hazim; Cuisset, Thomas

    2016-06-01

    The pharmacological management of patients with ST elevation myocardial infarction (STEMI) poses a significant challenge to the clinician. While mechanical reperfusion with primary percutaneous coronary intervention (PPCI) has proved its superiority over fibrinolysis, the best antithrombotic strategy surrounding the procedure remains a matter of debate. Due to the high risk of bleeding induced by antithrombotic drugs, the pharmacological management of STEMI needs to focus on an optimal strategy that reduces the rate of coronary thrombotic events without leading to excess bleeding. Intravenous anticoagulants are recommended for all patients presenting with STEMI. Low molecular heparin may be preferred over unfractionated heparin in the setting of PPCI. Recent data suggest that anticoagulation with bivalirudin can be utilized as an alternative strategy to heparin and Gp2b3a but this should be limited to patients at high risk of bleeding. Dual antiplatelet therapy comprising aspirin and P2Y12 inhibitor represents the cornerstone treatment for STEMI. New P2Y12 inhibitors (prasugrel and ticagrelor) have restricted clopidogrel use to situations where these potent agents are contraindicated. Whilst all oral antiplatelet agents have been used with an initial loading dose in STEMI, the time of their administration remains a controversial issue. In everyday practice, intravenous antiplatelet agents appear less consensual. While Gp2b3a receptor inhibitors use has been restricted to bailout situations, the place of cangrelor is not yet defined in real life daily practice. PMID:26934662

  19. Enhancement of photodynamic therapy effect by temporally inhibiting infarction with anticoagulant heparin

    NASA Astrophysics Data System (ADS)

    Yang, Liyong; Zhao, Hongyou

    2008-12-01

    Photodynamic Therapy (PDT) is one of the tumor-targeting therapeutics, and has been an established medical practice in recent years. PDT mediates tumor destruction mainly by killing tumor cells directly and damaging the tumor-associated vasculature, also inducing an immune response against tumor cells. For the Photofrin-mediated PDT, Vascular system injury is the predominant destruction that results in vascular collapse and blood plasma leakage, then leading to tumor infarction. However, thrombus formation during PDT may influence the light transmission and oxygen supply. Also some tumor cells not killed by PDT may irritate angiogenesis, causing the tumor recurrence under the condition of hypoxia after PDT. In our work, to prolong coagulation and formation of thrombus, an anticoagulant heparin was employed before the Photofrin-mediated PDT. After being administrated both Photofrin and anticoagulant heparin, the BALB/c mice with the subcutaneous EMT6 mammary carcinomas model were exposed to laser (635nm). And then an enhanced effect was received. Our experiments indicated that its antitumor effect may be attributed to the improvement of the light delivery to the deep part of tumor and oxygen supply for PDT. The results suggested that heparin can be used to enhance the effect of PDT in a solid tumor treatment.

  20. Monitoring anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome.

    PubMed

    Isert, Mecki; Miesbach, Wolfgang; Schüttfort, Gundolf; Weil, Yvonne; Tirneci, Vanessa; Kasper, Alexander; Weber, Adele; Lindhoff-Last, Edelgard; Herrmann, Eva; Linnemann, Birgit

    2015-08-01

    Because of the possible interference of antiphospholipid antibodies (APL) with the phospholipid component of thromboplastin reagents, concerns have been raised about the validity of international normalized ratio (INR) testing to monitor anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome (APS). To investigate the reliability of the INR, we determined the INR using various prothrombin time (PT) assays and compared the results with those of a chromogenic factor X (CFX) assay. The study cohort consisted of 40 APS patients and 100 APL-negative patients who were on anticoagulant therapy for reasons other than APS. The agreement (i.e. the percentage of patients with a difference ≤0.5 INR units) between the PT-derived INR and CFX-derived INR equivalents was only moderate in both patient groups. The best agreement with CFX-derived INR equivalents was observed for the Thromborel S reagent in APS patients (69.1 %) and for Neoplastin Plus in APL-negative patients (72.0 %). Regarding the results for the point-of-care system CoaguChek XS, an agreement between the INR and the CFX-derived INR equivalent was less frequently observed in the APS patients (55.6 vs. 67.8 %; p = 0.050). When considering all 3058 pairs of INR tests within the international sensitivity index (ISI)-calibrated range of 1.5 to 4.5 s, we did not observe a higher variability of INR values in either the APS patient group or the subgroup of APS patients positive for lupus coagulants compared with the APL-negative controls. In conclusion, monitoring vitamin K antagonists (VKA) therapy with laboratory INR measurements seems to be suitable for the majority of APS patients. PMID:25859986

  1. Clinical Factors and Perioperative Strategies Associated with Outcome in Preinjury Antiplatelet and Anticoagulation Therapy for Patients with Traumatic Brain Injuries

    PubMed Central

    Pang, Chang Hwan; Lee, Soo Eon

    2015-01-01

    Objective Long-term oral anticoagulation or antiplatelet therapy has been used with increasing frequency in the elderly. These patients are at increased risk of morbidity and mortality from expansion of intracranial hemorrhage. We conducted a single-center retrospective case control study to evaluate risk factors associated with outcomes and to identify the differences in outcome in traumatic brain injury between preinjury anticoagulation use and without anticoagulation. Methods A retrospective study of patients who underwent craniotomy or craniectomy for acute traumatic cerebral hemorrhage, between January 2005 and December 2014 was performed. Results A consecutive series of 50 patients were evaluated. The factors significantly differed between the two groups were initial Prothrombin Time-International Normalized Ratio, initial platelet count, initial Glasgow Coma Scale score, and postoperative intracranial bleeding. Mean Glasgow Outcome Scale (GOS) score were similar between the two groups. In the patient with low-energy trauma only, no significant differences in GOS score, postoperative bleeding and many other factors were observed. The contributing factors to postoperative bleeding was preinjury anticoagulation and its adjusted odds ratio was 12 [adjusted odds ratio (OR), 12.242; p=0.0070]. The contributing factors to low GOS scores, which mean unfavorable neurological outcomes, were age (adjusted OR, 1.073; p=0.039) and Rotterdam scale score for CT scans (adjusted OR, 3.123; p=0.0020). Conclusion Preinjury anticoagulation therapy contributed significantly to the occurrence of postoperative bleeding. However, preinjury anticoagulation therapy in the patients with low-energy trauma did not contribute to the poor clinical outcomes or total hospital stay. Careful attention should be given to older patients and severity of hemorrhage on initial brain CT. PMID:26539271

  2. Antiplatelet therapy strategies after percutaneous coronary intervention in patients needing oral anticoagulation.

    PubMed

    Saint Etienne, Christophe; Angoulvant, Denis; Simeon, Edouard; Fauchier, Laurent

    2013-11-01

    Long-term oral anticoagulant (OAC) and dual-antiplatelet therapy are commonly needed in patients with atrial fibrillation and in patients undergoing percutaneous coronary intervention (PCI), respectively. The combination of atrial fibrillation and PCI is frequent, and leads to a dilemma for antithrombotic therapy, where risk of stroke or stent thrombosis must be balanced with bleeding risk. In the WOEST study, 573 patients on OAC undergoing PCI were randomly assigned to receive clopidogrel alone or clopidogrel plus aspirin. The primary end point was the occurrence of any bleeding episode during 1-year follow-up. Clopidogrel alone administered to patients taking OAC after PCI was associated with a significantly lower rate of bleeding complications than clopidogrel plus aspirin. Moreover, a composite secondary end point of death, myocardial infarction and stent thrombosis was significantly lower in the dual-therapy group compared with the triple-therapy group. In spite of its limitations, the WOEST study constitutes a major breakthrough, showing that long-term aspirin after PCI may be obsolete in certain circumstances. This needs to be confirmed in further studies. PMID:24180531

  3. Decision-making about the use of non-vitamin K oral anticoagulant therapies for patients with atrial fibrillation.

    PubMed

    Eckman, Mark H

    2016-02-01

    Until recently, vitamin K antagonists, warfarin being the most commonly used agent in the United States, have been the only oral anticoagulant therapies available to prevent stroke in patients with atrial fibrillation (AF). In the last 5 years four new, non-vitamin K oral anticoagulants, the so-called NOACs or novel oral anticoagulants, have come to market and been approved by the Federal Drug Administration. Despite comparable if not superior efficacy in preventing AF-related stroke, and generally lower risks of major hemorrhage, particularly intracranial bleeding, the uptake of these agents has been slow. A number of barriers stand in the way of the more widespread use of these novel agents. Chief among them is concern about the lack of antidotes or reversal agents. Other concerns include the need for strict medication adherence, since missing even a single dose can lead to a non-anticoagulated state; out-of-pocket costs for patients; the lack of easily available laboratory tests to quantitatively assess the level of anticoagulant activity when these agents are being used; contraindications to use in patients with severe chronic kidney disease; and black-box warnings about the increased risk of thromboembolic events if these agents are discontinued prematurely. Fortunately, a number of reversal agents are in the pipeline. Three reversal agents, idarucizumab, andexanet alfa, and aripazine, have already progressed to human studies and show great promise as either antidotes for specific drugs or as universal reversal agents. The availability of these reversal agents will likely increase the clinical use of the non-vitamin K oral anticoagulants. In light of the many complex and nuanced issues surrounding the choice of an optimal anticoagulant for any AF patient, a patient-centered/shared decision-making approach will be useful. PMID:26343041

  4. External Beam Radiotherapy for Prostate Cancer Patients on Anticoagulation Therapy: How Significant is the Bleeding Toxicity?

    SciTech Connect

    Choe, Kevin S.; Jani, Ashesh B.; Liauw, Stanley L.

    2010-03-01

    Purpose: To characterize the bleeding toxicity associated with external beam radiotherapy for prostate cancer patients receiving anticoagulation (AC) therapy. Methods and Materials: The study cohort consisted of 568 patients with adenocarcinoma of the prostate who were treated with definitive external beam radiotherapy. Of these men, 79 were receiving AC therapy with either warfarin or clopidogrel. All patients were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Bleeding complications were recorded during treatment and subsequent follow-up visits. Results: With a median follow-up of 48 months, the 4-year actuarial risk of Grade 3 or worse bleeding toxicity was 15.5% for those receiving AC therapy compared with 3.6% among those not receiving AC (p < .0001). On multivariate analysis, AC therapy was the only significant factor associated with Grade 3 or worse bleeding (p < .0001). For patients taking AC therapy, the crude rate of bleeding was 39.2%. Multivariate analysis within the AC group demonstrated that a higher radiotherapy dose (p = .0408), intensity-modulated radiotherapy (p = 0.0136), and previous transurethral resection of the prostate (p = .0001) were associated with Grade 2 or worse bleeding toxicity. Androgen deprivation therapy was protective against bleeding, with borderline significance (p = 0.0599). Dose-volume histogram analysis revealed that Grade 3 or worse bleeding was minimized if the percentage of the rectum receiving >=70 Gy was <10% or the rectum receiving >=50 Gy was <50%. Conclusion: Patients taking AC therapy have a substantial risk of bleeding toxicity from external beam radiotherapy. In this setting, dose escalation or intensity-modulated radiotherapy should be used judiciously. With adherence to strict dose-volume histogram criteria and minimizing hotspots, the risk of severe bleeding might be reduced.

  5. Cost-Effectiveness of Thrombolytic Therapy, Compared with Anticoagulants Therapy in the Treatment of Acute Myocardial Infarction in Albania

    PubMed Central

    Rama, Mirvete; Miraci, Mirela; Balla, Idriz; Petrela, Ela; Malaj, Ledjan; Koleci, Anjeza

    2015-01-01

    AIM: The study aim is to evaluate the cost-effectiveness of thrombolytic treatment in acute MI comparing with anticoagulants therapy and between each other thrombolytic (SK, r-Pa). MATERIAL AND METHODS: We used a prospective registry of all patients admitted for acute myocardial infarction in intensive care units in Tirana. The average drugs cost was calculated for the hospitalization period in Albanian money (ALL). Survival and life quality were estimated by phone contact 1 year after acute MI. RESULTS: Anticoagulant group cost is 23865.3 ALL (170.5€), SK group cost is 54148.63 ALL (386.7€), r-Pa group has a cost of 92184.90 ALL (658.5€). In the group treated with SK the hospital survival is 100%, while in the control group 88.8%. Reteplase group has a lower period of stay in hospital than SK group 13.04 days vs. 17.97 days, mean age in group treated with r-Pa is 64.29 ± 10.03 approximate with anticoagulant group mean age 64.17 ± 11.08; differ significantly with SK group mean age 56.75 ± 10.04. Survival after 1 year was 96.4% for r-Pa and 96.9% SK. CONCLUSIONS: SK and r-Pa are successful thrombolytics with high effectiveness. It is gained a higher survival with the thrombolytic treatments. Reteplase is well tolerated in older patients than SK, is easier to apply than Streptokinase, but has higher cost. PMID:27275248

  6. A novel microfluidic anti-factor Xa assay device for monitoring anticoagulant therapy at the point-of-care

    NASA Astrophysics Data System (ADS)

    Harris, Leanne F.; Rainey, Paul; Castro-López, Vanessa; O'Donnell, James S.; Killard, Anthony J.

    2013-05-01

    Millions of patients worldwide are receiving anticoagulant therapy to treat hypercoagulable diseases. While standard testing is still performed in the central laboratory, point-of-care (POC) diagnostics are being developed due to the increasing number of patients requiring long-term anticoagulation and with a need for more personalized and targeted therapy. Many POC devices on the market focus on clot measurement, a technique which is limited in terms of variability, highlighting the need for more reliable assays of anticoagulant status. The anti-Xa assay, a factor specific optical assay, was developed to measure the extent to which exogenous factor Xa (FXa) is inhibited by heparinantithrombin complexes. We have developed a novel microfluidic device and assay for monitoring the effect of heparin anticoagulant therapy at the point-of-care. The assay which was also developed in our institute is based on the anti-Xa assay principle but uses fluorescence as the method of detection. Our device is a disposable laminate microfluidic strip, fabricated from the cyclic polyolefin (COP), Zeonor®, which is extremely suitable for application to fluorescent device platforms. We present data on the execution of the anti-Xa assay in this microfluidic format, demonstrating that the assay can be used to measure heparin in human plasma samples from 0 to 0.8 U/ml, with average assay reproducibility of 8% and a rapid result obtained within 60 seconds. Results indicate that with further development, the fluorogenic anti-Xa assay and device could become a successful method for monitoring anticoagulant therapy.

  7. Is Post-TIPS Anticoagulation Therapy Necessary in Patients with Cirrhosis and Portal Vein Thrombosis? A Randomized Controlled Trial.

    PubMed

    Wang, Zhu; Jiang, Ming-Shan; Zhang, Hai-Long; Weng, Ning-Na; Luo, Xue-Feng; Li, Xiao; Yang, Li

    2016-06-01

    Purpose To determine whether posttransjugular intrahepatic portosystemic shunt (TIPS) placement anticoagulation therapy could benefit patients with cirrhosis and portal vein thrombosis (PVT) from the perspective of a change in portal vein patency status and clinical outcomes. Materials and Methods The study was approved by the institutional review board, and informed consent was obtained from each patient. From October 2012 to February 2014, patients with cirrhosis and PVT who underwent TIPS placement were randomly assigned to the anticoagulation therapy or control group. All patients were followed at 1, 3, 6, and 12 months after the TIPS procedure. Outcome measures were a change of portal vein patency status and clinical measures including gastrointestinal rebleeding, shunt dysfunction, hepatic encephalopathy, and survival. Student t test, χ(2) test, Fisher exact test, Mann-Whitney U test, and logistical regression were applied where appropriate. Results A total of 64 patients were enrolled in the study, with 31 allocated to the anticoagulation group and 33 allocated to the control group. Overall, thrombi were improved in 61 patients (96.8%) after the procedure. PVT recanalization (ie, complete disappearance; reconstruction of cavernous transformation) was achieved in 26 patients (83.9%) in the anticoagulation therapy group and in 23 (71.8%) patients in tthe control group (P = .252). The presence of a superior mesenteric vein thrombus may help predict recanalization failure (unadjusted relative risk = 0.243; 95% confidence interval: 0.070, 0.843; P = .026). Clinical outcomes were also similar between the two groups. Conclusion Anticoagulation therapy may not be necessary in certain patients with PVT because TIPS placement alone can achieve a high persistent recanalization rate. (©) RSNA, 2015. PMID:26653681

  8. Intracerebral Hematoma Occurring During Warfarin Versus Non-Vitamin K Antagonist Oral Anticoagulant Therapy.

    PubMed

    Takahashi, Haruhiko; Jimbo, Yasushi; Takano, Hiroki; Abe, Hiroshi; Sato, Masahito; Fujii, Yukihiko; Aizawa, Yoshifusa

    2016-07-15

    The neuroradiological findings and its outcomes of intracerebral hemorrhage (ICH) were compared between the non-vitamin K antagonist oral anticoagulant (NOAC) therapy and warfarin therapy. In the latest 3 years, 13 cases of nonvalvular atrial fibrillation on NOAC therapy were admitted for ICH. For comparison, 65 age- and gender-comparable patients with ICH on warfarin therapy were recruited. Three NOACs had been prescribed: dabigatran (n = 4), rivaroxaban (n = 2), and apixaban (n = 7). The average ages were 76 ± 9 and 78 ± 8 years in the warfarin (n = 65) and NOAC groups (n = 13), respectively. There was no difference in the clinical features, including the CHADS2 score or HAS-BLED score: 2.62 ± 1.31 versus 2.62 ± 1.33, or 1.09 ± 0.43 versus 1.00 ± 0.41, for the warfarin and NOAC groups, respectively. The volume of ICH <30 ml was found in 84.6% of the patients on NOACs, but it was found in 53.8% of the patients on warfarin (p = 0.0106). The expansion of hematoma was limited to 7 patients (10.8%) of the warfarin group. A lower hospital mortality and better modified Rankin Scale were observed in the NOAC group than in the warfarin group: 1 (7.7%) versus 27 (41.5%; p = 0.0105) and 3.2 ± 1.4 versus 4.5 ± 1.6 (p = 0.0057), respectively. In conclusion, ICH on NOAC therapy had smaller volume of hematoma with reduced rate of expansion and decreased mortality compared with its occurrence on warfarin. PMID:27289294

  9. Profile and anticoagulation outcomes of patients on warfarin therapy in an urban hospital in Cape Town, South Africa

    PubMed Central

    Hellenberg, Derek A.; Cupido, Clint S.; Jaeger, Cilia

    2016-01-01

    Background Warfarin is the most frequently used oral anticoagulant worldwide and it is the oral anticoagulant of choice in South Africa for reducing thrombosis-related morbidity and mortality. However, the safety and efficacy of warfarin therapy depends mainly on careful monitoring and maintenance of the international normalised ratio (INR) within an optimal therapeutic range. Aim The aim of this study was to describe the profile and the anticoagulation outcomes of patients on warfarin therapy in a major warfarin clinic in the Western Cape Province of South Africa. Setting Victoria Hospital - a district hospital in Cape Town. Methods A cross sectional review of clinical records of patients on warfarin therapy who attended the INR clinic from 01 January 2014 to 30 June 2014 was done. Data analysis was done with STATA to generate appropriate descriptive data. Results Our study showed that atrial fibrillation (AF) was the commonest indication for warfarin use in this study and hypertension was the commonest comorbidity among these patients. Only 48.5% achieved target therapeutic range; 51.5% were out-of-range. There was a significant association between alcohol consumption and poor anticoagulation outcomes (p-value < 0.022). Anticoagulation outcomes were better among the older age groups, male patients and in those with AF. The prevalence of thrombotic events while on warfarin treatment was 2.2%, while prevalence of haemorrhagic events was 14%. Most of the patients with bleeding events were on concurrent use of warfarin and other medications with potential drug interactions. Conclusion In our study, patients who achieved target therapeutic control were less than the acceptable 60%. PMID:27247158

  10. Management of anticoagulant therapy during pregnancy in patients with prosthetic heart valves

    PubMed Central

    Jenkins, B. Stephen; Braimbridge, Mark V.

    1971-01-01

    We describe two patients with Starr-Edwards mitral valve replacements who underwent pregnancy on oral anticoagulants and who were successfully delivered of live babies. The literature on pregnancy with prosthetic heart valves is reviewed. It is suggested that properly controlled oral anticoagulation should be continued until the onset of labour; the anticoagulant effect should then be reversed by an intravenous infusion of fresh-frozen plasma and the patient maintained on intravenous heparin injections six-hourly. Oral anticoagulants should be restarted immediately after delivery and the heparin withdrawn only when their effect has been re-established. PMID:5576538

  11. Use of Oral Anticoagulation Therapy in Atrial Fibrillation after Stroke: Results from a Nationwide Registry

    PubMed Central

    Jespersen, Stine Funder; Christensen, Louisa M.; Christensen, Anders; Christensen, Hanne

    2013-01-01

    Background. The knowledge is still sparse about patient related factors, influencing oral anticoagulation therapy (OAC) rates, in stroke patients with atrial fibrillation (AF). Aims. To assess the use of OAC in ischemic stroke patients diagnosed with AF and to identify patient related factors influencing the initiation of OAC. Methods. In the nationwide Danish Stroke Registry we identified 55,551 patients admitted with acute ischemic stroke from 2003 to 2011. Frequency analysis was used to assess the use of OAC in patients with AF, and logistic regression was used to determine independent predictors of OAC. Results. 17.1% (n = 9,482) of ischemic stroke patients had AF. OAC prescription rates were increasing, and in 2011 46.6% were prescribed OAC, 42.5% had a contraindication, and 3.7% were not prescribed OAC without a stated contraindication. Younger age, less severe stroke, and male gender were positive predictors of OAC, while excessive alcohol consumption, smoking, and institutionalization were negative predictors of OAC (P values < 0.05). Conclusions. Advanced age, severe stroke, female gender, institutionalization, smoking, and excessive alcohol consumption were associated with lower OAC rates. Contraindications were generally present in patients not in therapy, and the assumed underuse of OAC may be overestimated. PMID:24349774

  12. A Proposal for an Individualized Pharmacogenetic-Guided Warfarin Dosage Regimen for Puerto Rican Patients Commencing Anticoagulation Therapy

    PubMed Central

    Bosch, Luis Ángel Bermúdez

    2014-01-01

    Warfarin is the current standard of care in oral anticoagulation therapy. It is commonly prescribed to treat venous thromboembolism, pulmonary embolism, acute myocardial infarction, and to decrease the risk of stroke in atrial fibrillation. Warfarin therapy is challenging because of marked and often unpredictable inter-individual dosing variations that effectively reach and maintain adequate anticoagulation. Several researchers have developed pharmacogenetic-guided maintenance dose algorithms that incorporate genetics and individual patient characteristics. However, there is limited information available concerning dosing during warfarin initiation. This is considered the most clinically challenging therapeutic phase. In such, the risk of recurrent thromboembolism and hemorrhage are elevated. The objective of this retrospective study is to predict the individual initial doses for Puerto Rican patients (n=175) commencing anticoagulation therapy at Veterans Affairs Caribbean Healthcare System (VACHS) using pharmacogenetic/pharmacokinetic-driven model. A pharmacogenetic driven model (R2=0.4809) was developed in Puerto Rican patients and combined with pharmacokinetic formulas that enabled us to predict the individual initial doses for patients (n=121) commencing anticoagulation therapy. WinNonlin® pharmacokinetic-pharmacodynamic simulations were carried out to determine the predictability of this model. This model demonstrated promising results with few (n=10) simulations outside of their respective therapy range. A customized pharmacogenetic-based warfarin maintenance dose algorithm (R2=0.7659) was developed in a derivation cohort of 131 patients. The predictability of this developed pharmacogenetic algorithm was compared with the International Warfarin Pharmacogenomics Consortium (IWPC) algorithm and it demonstrated superior predictability within our study population. PMID:25285240

  13. Oral Anticoagulant Therapy and Bleeding Events with Vitamin K Antagonists in Patients with Atrial Fibrillation in a Hungarian County Hospital

    PubMed Central

    Mark, Laszlo; Dani, Győző; Vendrey, Robert; Paragh, György; Katona, Andras

    2015-01-01

    Background Vitamin K antagonists, despite their tight therapeutic spectrum and the fear of bleeding complications, were long the most important drugs used in anticoagulant therapy. The aim of this study was to evaluate the quality of anticoagulant therapy and its relation with bleedings in everyday clinical practice. Material/Methods We analyzed the data of 272 patients with non-valvular atrial fibrillation treated in our county hospital using retrospective data collection of the last 1008±384 days. The INR (International Normalized Ratio) values and the time in therapeutic range (TTR) were analyzed. We asked patients about bleeding complications and searched the medical records. Results The TTR proved to be 64% and there was no statistically significant difference between that of 252 (92.7%) patients taking acenocoumarol and 20 (7.3%) on warfarin. Analyzing various factors leading to TTR under 70%, we found that none of them have a significant impact. Significantly more bleeding events occurred in the first 3 months after the initiation of anticoagulant therapy and in patients with TTR under 70%, but the latter was not significant after adjustment for factors influencing bleeding (OR 1.607, CI 0.571–4.522, p=0.392). Conclusions Although the present study’s TTR values were similar to those found in the warfarin branch of various large-scale international trials and in real-life settings, further improvement of vitamin K antagonist therapy are necessary. As the possibilities for this are limited, we believe that the new type anticoagulant agents have a place in everyday clinical practice. PMID:25686556

  14. Protein C deficiency related obscure gastrointestinal bleeding treated by enteroscopy and anticoagulant therapy

    PubMed Central

    Hsu, Wei-Fan; Tsang, Yuk-Ming; Teng, Chung-Jen; Chung, Chen-Shuan

    2015-01-01

    Obscure gastrointestinal bleeding is an uncommonly encountered and difficult-to-treat clinical problem in gastroenterology, but advancements in endoscopic and radiologic imaging modalities allow for greater accuracy in diagnosing obscure gastrointestinal bleeding. Ectopic varices account for less than 5% of all variceal bleeding cases, and jejunal variceal bleeding due to extrahepatic portal hypertension is rare. We present a 47-year-old man suffering from obscure gastrointestinal bleeding. Computed tomography of the abdomen revealed multiple vascular tufts around the proximal jejunum but no evidence of cirrhosis, and a visible hypodense filling defect suggestive of thrombus was visible in the superior mesenteric vein. Enteroscopy revealed several serpiginous varices in the proximal jejunum. Serologic data disclosed protein C deficiency (33.6%). The patient was successfully treated by therapeutic balloon-assisted enteroscopy and long-term anticoagulant therapy, which is normally contraindicated in patients with gastrointestinal bleeding. Diagnostic modalities for obscure gastrointestinal bleeding, such as capsule endoscopy, computed tomography enterography, magnetic resonance enterography, and enteroscopy, were also reviewed in this article. PMID:25624741

  15. Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant

    PubMed Central

    Glueck, Charles J.; Lee, Kevin; Prince, Marloe; Jetty, Vybhav; Shah, Parth; Wang, Ping

    2016-01-01

    Background: When exogenous testosterone or treatments to elevate testosterone (human chorionic gonadotropin [HCG] or Clomid) are prescribed for men who have antecedent thrombophilia, deep venous thrombosis and pulmonary embolism often occur and may recur despite adequate anticoagulation if testosterone therapy is continued. Case Presentation: A 55-year-old white male was referred to us because of 4 thrombotic events, 3 despite adequate anticoagulation over a 5-year period. We assessed interactions between thrombophilia, exogenous testosterone therapy, and recurrent thrombosis. In 2009, despite low-normal serum testosterone 334 ng/dL (lower normal limit [LNL] 300 ng/dL), he was given testosterone (TT) cypionate (50 mg/week) and human chorionic gonadotropin (HCG; 500 units/week) for presumed hypogonadism. Ten months later, with supranormal serum T (1385 ng/dL, upper normal limit [UNL] 827 ng/dL) and estradiol (E2) 45 pg/mL (UNL 41 pg/mL), he had a pulmonary embolus (PE) and was then anticoagulated for 2 years (enoxaparin, then warfarin). Four years later, on TT-HCG, he had his first deep venous thrombosis (DVT). TT was stopped and HCG continued; he was anticoagulated (enoxaparin, then warfarin, then apixaban, then fondaparinux). One year after his first DVT, on HCG, still on fondaparinux, he had a second DVT (5/315), was anticoagulated (enoxaparin + warfarin), with a Greenfield filter placed, but 8 days later had a second PE. Thrombophilia testing revealed the lupus anticoagulant. After stopping HCG, and maintained on warfarin, he has been free of further DVT-PE for 9 months. Conclusion: When DVT-PE occur on TT or HCG, in the presence of thrombophilia, TT-HCG should be stopped, lest DVT-PE reoccur despite concurrent anticoagulation. PMID:27536705

  16. Patients’ perspectives regarding long-term warfarin therapy and the potential transition to new oral anticoagulant therapy

    PubMed Central

    Gebler-Hughes, Elizabeth S.; Kemp, Linda

    2014-01-01

    Objectives: To examine patients’ perspectives regarding long-term vitamin K antagonist (VKA) therapy and the potential transition to new oral anticoagulants (NOACs) such as dabigatran and rivaroxaban, and to determine if factors such as residential location affect these opinions. Design, setting and participants: Patients on VKA therapy for at least 12 weeks completed a questionnaire specifically designed for the study. They were recruited while attending point-of-care international normalized ratio (INR) testing at six South Australian general practice clinics during the period July–September 2013. Main outcome measures: Opinions of current VKA therapy, level of awareness of NOACs, and ratings of potential benefits and deterrents of transition to NOACs were sought. Results: Data from 290 participants were available for analysis (response rate 95.4%). The majority of the sample (79.5%, 229/288) were either satisfied or very satisfied with current VKA therapy. The mean score for the potential benefits of transition to NOACs was 7.6 (±4.2) out of a possible 20, which was significantly lower than the mean score 10.9 (±4.5) for the perceived deterrents to transition (p < 0.001). Rural patients (82.0%, 82/100) were significantly more likely (p = 0.001) to have not heard of NOACs than metropolitan patients (50.3%, 95/189) and also perceived significant less benefits in a transition to NOACs (p = 0.001). Conclusion: When considering potential transition from VKAs to NOACs it is important for prescribers to consider that some patients, in particular those from a rural location, may not perceive a significant benefit in transitioning or may have particular concerns in this area. PMID:25436104

  17. Whose preferences should be elicited for use in health-care decision-making? A case study using anticoagulant therapy.

    PubMed

    Mott, David John; Najafzadeh, Mehdi

    2016-01-01

    The question of whose preferences to elicit in health-state valuation has been widely discussed in the literature. The importance of this debate lies in the fact that health-state utility values are used in health technology assessment (HTA); therefore, an individual's preferences can influence decision-making. If preferences differ across groups, making decisions based on one group's preferences may be suboptimal for the other. Preferences for benefits, risks, experiences and health states associated with anticoagulant therapies have been elicited by researchers due to the underutilization of warfarin and the introduction of non-vitamin K antagonist oral anticoagulants. The majority of existing studies elicit preferences from patient populations as opposed to other stakeholders such as the general public. This paper extends the preference debate by using this clinical area as a case study, with a particular focus on HTA guidelines and the recent advocacy of the use of preference information in benefit-risk assessments. PMID:26560704

  18. Can the vicious cycle of obscure or intractable gastrointestinal bleeding be broken in patients with atrial fibrillation subject to anticoagulant therapy?

    PubMed

    Fernández-Rodríguez, Diego; Martín-Yuste, Victoria; Feu, Faust; Brugaletta, Salvatore; Freixa, Xavier; Regueiro, Ander; Sabaté, Manel

    2014-05-01

    Gastrointestinal bleeding of obscure origin or with an intractable cause is particularly common in patients with atrial fibrillation subject to oral anticoagulant therapy. This condition is highly recurrent and therefore gives rise to high morbidity and mortality rates, thus entailing a vicious cycle that is difficult to solve.Percutaneous left atrial appendage closure has become a therapeutic alternative for patients with atrial fibrillation and a contraindication for oral anticoagulation. This technique would allow the discontinuation of oral anticoagulants, thus helping to reduce the risk for gastrointestinal bleeding, and would also be protective against embolic events in this group of patients, thereby eventually breaking this vicious cycle.We report our experience with percutaneous left atrial appendage closure in the management of patients with atrial fibrillation who are subject to oral anticoagulation therapy and suffer from obscure or intractable gastrointestinal bleeding. PMID:25287239

  19. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines

    PubMed Central

    Veitch, Andrew M; Vanbiervliet, Geoffroy; Gershlick, Anthony H; Boustiere, Christian; Baglin, Trevor P; Smith, Lesley-Ann; Radaelli, Franco; Knight, Evelyn; Gralnek, Ian M; Hassan, Cesare; Dumonceau, Jean-Marc

    2016-01-01

    The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage versus thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor) For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation); For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation). For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). Warfarin The advice for warfarin is fundamentally unchanged from British Society of Gastroenterology (BSG) 2008 guidance. Direct Oral Anticoagulants (DOAC) For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation); For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken ≥48 h before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30–50 mL/min we recommend that the last dose of DOAC be taken 72 h before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation). PMID:26873868

  20. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines.

    PubMed

    Veitch, Andrew M; Vanbiervliet, Geoffroy; Gershlick, Anthony H; Boustiere, Christian; Baglin, Trevor P; Smith, Lesley-Ann; Radaelli, Franco; Knight, Evelyn; Gralnek, Ian M; Hassan, Cesare; Dumonceau, Jean-Marc

    2016-04-01

    The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage vs. thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor): For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation);For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation).For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). Warfarin: The advice for warfarin is fundamentally unchanged from BSG 2008 guidance. Direct Oral Anticoagulants (DOAC): For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation). For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken ≥ 48 hours before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30 - 50 mL/min we recommend that the last dose of DOAC be taken 72 hours before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation). PMID:26890676

  1. Impact of renal function deterioration on adverse events during anticoagulation therapy using non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

    PubMed

    Miyamoto, Koji; Aiba, Takeshi; Arihiro, Shoji; Watanabe, Makoto; Kokubo, Yoshihiro; Ishibashi, Kohei; Hirose, Sayako; Wada, Mitsuru; Nakajima, Ikutaro; Okamura, Hideo; Noda, Takashi; Nagatsuka, Kazuyuki; Noguchi, Teruo; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kamakura, Shiro; Shimizu, Wataru; Miyamoto, Yoshihiro; Toyoda, Kazunori; Kusano, Kengo

    2016-08-01

    Renal function is crucial for patients with non-valvular atrial fibrillation (NVAF) using non-vitamin K antagonist oral anticoagulants (NOAC). The incidence of renal function deterioration during anticoagulation therapy and its impact of adverse events are unknown. In 807 consecutive NVAF patients treated with NOAC and with estimated creatinine clearance (eCCr) ≥ 50 ml/min (mean age 68 ± 11 years, mean CHADS2 score = 1.8 ± 1.4, CHA2DS2-VASc score = 2.8 ± 1.8, HAS-BLED score = 1.7 ± 1.1), we analyzed the time course of renal function and clinical outcomes, and compared these with the data of general Japanese inhabitants from the Suita Study (n = 2140). Of the 807 patients, 751 (93 %) maintained eCCr ≥ 50 ml/min (group A) whereas the remaining 56 (7 %) fell into the eCCr < 50 ml/min (group B) during the 382 ± 288 days of follow-up. Multivariate logistic regression analysis revealed that advanced age, lower body weight, and congestive heart failure were independent predictors for renal function deterioration in patients with eCCr ≥ 50 ml/min at baseline. Major and/or minor bleedings were more commonly observed in group B than in group A (21 vs. 8 %; P = 0.0004). The CHADS2, CHA2DS2-VASc, and HAS-BLED scores were also significant predictors of renal function deterioration (P < 0.0001). The incidences of renal function deterioration were 1.4, 3.4, 10.5 and 11.7 % in patients with CHADS2 score of 0, 1, 2 and ≥3, respectively. As to CHA2DS2-VASc score, renal function deterioration occurred in 0, 1.7, 9.8 and 15.0 % with a score of 0, 1-2, 3-4 and ≥5, respectively. In the Suita Study of the general population, on the other hand, 122 of 2140 participants with eCCr ≥ 50 ml/min at baseline (5.7 %) fell into the eCCr < 50 ml/min during about 2 years. The incidence of renal function deterioration increased with the CHADS2 score in the general population as well as in our patients. Renal function deterioration was

  2. Effects of Oral Anticoagulant Therapy in Medical Inpatients ≥65 Years With Atrial Fibrillation.

    PubMed

    Bo, Mario; Sciarrillo, Irene; Li Puma, Federica; Badinella Martini, Marco; Falcone, Yolanda; Iacovino, Marina; Grisoglio, Enrica; Menditto, Elena; Fonte, Gianfranco; Brunetti, Enrico; Maggiani, Guido; Isaia, Giovanni Carlo; Gaita, Fiorenzo

    2016-02-15

    In this retrospective cohort observational study, we investigated mortality, ischemic, and hemorrhagic events in patients ≥65 years with atrial fibrillation consecutively discharged from an Acute Geriatric Ward in the period 2010 to 2013. Stroke and bleeding risk were evaluated using CHA2DS2-VASC (congestive heart failure/left ventricular dysfunction, hypertension, aged ≥75 years, diabetes mellitus, stroke/transient ischemic attack/systemic embolism, vascular disease, aged 65 to 74 years, gender category) and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) scores. Co-morbidity, cognitive status, and functional autonomy were evaluated using standardized scales. Independent associations among clinical variables, including use of vitamin K antagonist-based oral anticoagulant therapy (OAT), all-cause mortality, and fatal and nonfatal ischemic and hemorrhagic events, were evaluated. Further clinical outcomes comparison between patients treated with OAT and those untreated was performed after adjustment for significant differences in patient baseline characteristics with propensity score matching. Of 980 patients discharged (mean age 83 years, 60% women, roughly 30% cognitively impaired or functionally dependent, mean CHA2DS2-VASC and HAS-BLED scores 4.8 and 2.1, respectively), 505 (51.5%) died during a mean follow-up period of 571 days; ischemic and hemorrhagic stroke occurred in 82 (12.3%) and 13 patients (1.3%), respectively, and major bleedings in 43 patients (4.4%). Vitamin K antagonists' use was independently associated with reduced mortality (odds ratio 0.524) and with a nonsignificant reduction in incidence of ischemic stroke, without excess in bleeding risk. Similar findings were observed in the 2 propensity score-matched cohorts of patients. In conclusion, among vulnerable patients with atrial fibrillation ≥65 years with high

  3. Are there a guidelines for implantable spinal cord stimulator therapy in patients using chronic anticoagulation therapy? - A review of decision-making in the high-risk patient

    PubMed Central

    Ghaly, Ramsis F.; Lissounov, Alexei; Candido, Kenneth D.; Knezevic, Nebojsa Nick

    2016-01-01

    Background: Spinal cord stimulators (SCSs) are gaining increasing indications and utility in an expanding variety of clinical conditions. Complications and initial expenses have historically prevented the early use of SCS therapy despite ongoing efforts to educate and promote its utilization. At present, there exists no literature evidence of SCS implantation in a chronically anticoagulated patient, and neuromodulation manufacturers are conspicuously silent in providing warnings or recommendations in the face of anticoagulant use chronically. It would appear as through these issues demand scrutiny and industry as well as neuromodulation society advocacy and support in terms of the provision of coherent guidelines on how to proceed. Case Description: A 79-year-old male returned to the neurosurgical clinic with persistent low back pain and leg heaviness due to adjacent level degenerative spondylosis and severe thoracic spinal stenosis. The patient had a notable history of multiple comorbidities along with atrial fibrillation requiring chronic anticoagulation. On initial presentation, he was educated with three choice of conservative medical therapy, intrathecal drug delivery system implantation, or additional lumbar decompression laminectomy with instrumented fusion of T10-L3 and a palliative surgical lead SCS implantation. Description: A 79-year-old male returned to the neurosurgical clinic with persistent low back pain and leg heaviness due to adjacent level degenerative spondylosis and severe thoracic spinal stenosis. The patient had a notable history of multiple comorbidities along with atrial fibrillation requiring chronic anticoagulation. On initial presentation, he was educated with three choice of conservative medical therapy, intrathecal drug delivery system implantation, or additional lumbar decompression laminectomy with instrumented fusion of T10-L3 and a palliative surgical lead SCS implantation. Conclusion: Our literature search did not reveal any

  4. Current Perioperative Management of Anticoagulant and Antiplatelet Use in Neuroendovascular Therapy: Analysis of JR-NET1 and 2

    PubMed Central

    ENOMOTO, Yukiko; YOSHIMURA, Shinichi; SAKAI, Nobuyuki; EGASHIRA, Yusuke

    2014-01-01

    To evaluate current perioperative antithrombotic management in neuroendovascular therapy in Japan, we analyzed perioperative anticoagulant and antiplatelet use in various procedures and examined their relationships with periprocedural adverse events. Patient's data from nationwide surveys administered by the Japanese Registry of Neuroendovascular Therapy (JR-NET) between January 2005 and December 2007 (JR-NET1) and January 2008 and December 2009 (JR-NET2) were retrospectively analyzed. Compared to JR-NET1, the frequency of perioperative antiplatelet therapy and dual or triple therapy were increased for either aneurysm coiling and percutaneous transluminal angioplasty or stenting in JR-NET2. Although ischemic complications were significantly decreased (4.2% vs. 2.1%, p < 0.001), hemorrhagic complications (2.1% vs. 5.3%, p < 0.001), severe adverse events (1.5% vs. 2.1%, p < 0.001), and total perioperative complications (8.3% vs. 10.3%, p < 0.001) were significantly increased in JR-NET2. The rate of hemorrhagic complications was significantly higher in patients with triple or more perioperative antiplatelet therapy (preoperative: 5.3% vs. 9.2%, p < 0.0001, postoperative: 5.7% vs. 12.7%, p < 0.0001). Perioperative antithrombotic therapy was performed more frequently and intensively in neuroendovascular therapy in Japan. While ischemic complications were decreased, hemorrhagic complications and severe adverse events were increased. These results suggest that intensive antithrombotic therapy has a potential risk of hemorrhagic complications for Japanese patients. PMID:24305029

  5. [Therapy education for patients receiving oral anti-coagulants vitamin K antagonists].

    PubMed

    Satger, Bernadette; Blaise, Sophie; Fontaine, Michèle; Yver, Jacqueline; Allenet, Benoît; Baudrant, Magali; Pernod, Gilles; Bosson, Jean-Luc

    2009-12-01

    The vitamin K antagonists (VKA) remain to this day the only oral form of therapeutic anticoagulation. Approximately 1% of the French population, mainly elderly, is treated with these anticoagulants. Oral anticoagulants have significant risks of iatrogenic complications; indeed they are the leading cause of such drug-induced complications, predominantly hemorrhages. AFSSAPS (French Drug and Medical Products Agency) clinical practice recommendations, repeatedly disseminated, emphasize the education of patients receiving VKAs. Managing oral anticoagulant treatment is challenging, with a significant risk of under- or overdosing and consequently, thrombosis or hemorrhage. The therapeutic window is narrow, multiple drug-interactions are possible, and the specific dose required for a particular individual to achieve appropriate International Normalized Ratio (INR) levels is unpredictable. The literature contains few randomized controlled trials about the efficacy of education for patients treated with oral anticoagulants. These education programs are not standardized and are therefore varied and difficult to compare. Nevertheless, studies demonstrate the importance of patient education programs in reducing the risk of hemorrhage and achieving better treatment stability. The Grenoble region hospital-community network for vascular diseases (GRANTED) has developed an education program for these patients, consisting of individual sessions for the patient and/or a friend or family member (either at a health care facility or at the patient's home), telephone support and group sessions, and using educational tools and supports. There is also a link with the general practitioner who receives a report. This approach makes it possible to adapt the educational message to individual patients and their daily lives, as well as directly involving them in the management of their treatment. PMID:19815369

  6. Incidence, clinical impact and risk of bleeding during oral anticoagulation therapy

    PubMed Central

    Rubboli, Andrea; Becattini, Cecilia; Verheugt, Freek WA

    2011-01-01

    Bleeding is the most important complication of oral anticoagulation (OAC) with vitamin K-antagonists. Whilst bleeding is unavoidably related to OAC, it may have a great impact on the prognosis of treated subjects by leading to discontinuation of treatment, permanent disability or death. The yearly incidence of bleeding during OAC is 2%-5% for major bleeding, 0.5%-1% for fatal bleeding, and 0.2%-0.4% for intracranial bleeding. While OAC interruption and/or antagonism, as well as administration of coagulation factors, represent the necessary measures for the management of bleeding, proper stratification of the individual risk of bleeding prior to start OAC is of paramount importance. Several factors, including advanced age, female gender, poor control and higher intensity of OAC, associated diseases and medications, as well as genetic factors, have been proven to be associated with an increased risk of bleeding. Most of these factors have been included in the development of bleeding prediction scores, which should now be used by clinicians when prescribing and monitoring OAC. Owing to the many limitations of OAC, including a narrow therapeutic window, cumbersome management, and wide inter- and intra-individual variability, novel oral anticoagulants, such as factor Xa inhibitors and direct thrombin inhibitors, have been recently developed. These agents can be given in fixed doses, have little interaction with foods and drugs, and do not require regular monitoring of anticoagulation. While the novel oral anticoagulants show promise for effective thromboprophylaxis in atrial fibrillation and venous thromboembolism, definitive data on their safety and efficacy are awaited. PMID:22125670

  7. Long Standing Eculizumab Treatment without Anticoagulant Therapy in High-Risk Thrombogenic Paroxysmal Nocturnal Hemoglobinuria

    PubMed Central

    Al-Jafar, Hassan A.; AlDallal, Salma M.; Askar, Haifa A.; Aljeraiwi, Ali M.; Al-Alansari, Ahmad

    2015-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-orphan disease affecting all hematopoietic cell types. The abnormality of red blood cells in this disease predisposes to intravascular complement-mediated hemolysis. Eculizumab is an orphan drug used to treat this rare disease. Thrombosis is the key cause of death in PNH patients in about 40% to 67% of cases. We report the case of a woman presenting with PNH complicated with serious Budd-Chiari syndrome thrombosis and with a stent inserted in the portal vein. She refused to take any anticoagulant treatment since she commenced eculizumab 4 years before. No thrombotic events happened since that time. This case could add an extra benefit for eculizumab, which could be used as an anti-thromboembolic prophylactic agent in PNH, especially in patients with thrombocytopenia, where the use of anticoagulant agents is extremely hazardous. More randomized studies might establish the use of eculizumab without anticoagulants to avoid serious bleeding that could happen in thrombocytopenic PNH patients. PMID:26487933

  8. Racial Differences in Quality of Anticoagulation Therapy for Atrial Fibrillation (from the TREAT-AF Study).

    PubMed

    Yong, Celina; Azarbal, Farnaz; Abnousi, Freddy; Heidenreich, Paul A; Schmitt, Susan; Fan, Jun; Than, Claire T; Ullal, Aditya J; Yang, Felix; Phibbs, Ciaran S; Frayne, Susan M; Ho, P Michael; Shore, Supriya; Mahaffey, Kenneth W; Turakhia, Mintu P

    2016-01-01

    The influence of race on quality of anticoagulation control is not well described. We examined the association between race, international normalized ratio (INR) monitoring intensity, and INR control in warfarin-treated patients with atrial fibrillation (AF). Using data from the Veterans Health Administration (VHA), we performed a retrospective cohort study of 184,161 patients with a new diagnosis of AF/flutter from 2004 to 2012 who received any VHA prescription within 90 days of diagnosis. The primary predictor was race, ascertained from multiple VHA and linked Medicare demographic files. The primary outcome was first-year and long-term time in therapeutic range (TTR) of INR 2.0 to 3.0. Secondary outcomes were INR monitoring intensity and warfarin persistence. Of the 116,021 patients who received warfarin in the cohort, INR monitoring intensity was similar across racial groups. However, TTR was lowest in blacks and highest in whites (first year 0.49 ± 0.23 vs 0.57 ± 0.21, p <0.001; long term 0.52 ± 0.20 vs 0.59 ± 0.18, p <0.001); 64% of whites and 49% of blacks had long-term TTR >55% (p <0.001). After adjusting for site and patient-level covariates, black race was associated with lower first-year and long-term TTRs (4.2% and 4.1% below the conditional mean, relative to whites; p <0.0001 for both). One-year warfarin persistence was slightly lower in blacks compared to whites (58% vs 60%, p <0.0001). In conclusion, in patients with AF anticoagulated with warfarin, differences in INR control are most evident among blacks, underscoring the need to determine if other types of intensive management or warfarin alternatives may be necessary to improve anticoagulation among vulnerable AF populations. PMID:26552504

  9. [New anticoagulants].

    PubMed

    Bauersachs, R M

    2008-02-01

    This review updates the latest developments concerning new anticoagulants. It describes potential targets in the coagulation pathway: inhibition of the initiation of coagulation, factor Xa and thrombin inhibitors. The focus is laid on substances in late development that already passed the phase II trial for venous thromboembolism (VTE)-prevention as "proof of concept". In the group of factor Xa inhibitors, the indirect inhibitor Fondaparinux has got approval for the indications prevention and therapy of VTE and acute coronary syndromes (OASIS 5 and 6). Rivaroxaban is the first direct factor Xa inhibitor that was admitted for approval in the indication VTE-prevention. The first trial of the program RECORD 1-4 was finished, trials for the indications therapy of VTE (EINSTEIN) and stroke prevention in atrial fibrillation (ROCKET AF) are in phase III. The use in acute coronary symptoms is - like apixaban - evaluated in phase II. The ADOPT trial with apixaban for VTE-prevention, as well as the BOTTICELLI trial for atrial fibrillation, have reached phase III. After the withdrawal of Ximelagatran, Dabigatran is the most developed direct thrombin inhibitor, being extensively studied in the comprehensive phase- III-program REVOLUTION and in approval for the indication VTE-prevention. PMID:18278158

  10. New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis

    PubMed Central

    Oldgren, Jonas; Wallentin, Lars; Alexander, John H.; James, Stefan; Jönelid, Birgitta; Steg, Gabriel; Sundström, Johan

    2013-01-01

    Background Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting. Methods and results All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7–14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59–0.84], but increased clinically significant bleeding (HR: 1.79; 1.54–2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80–0.95), but more than doubled the bleeding (HR: 2.34; 2.06–2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies. Conclusion In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with

  11. Detecting nonvalvular atrial fibrillation and anticoagulant therapy in cardioembolic ischemic stroke.

    PubMed

    Min, Jiangyong; Farooq, Muhammad Umar

    2016-08-01

    Nonvalvular Atrial fibrillation (NVAF) is the most common cardiac arrhythmia associated with an increase in risk of stroke and systemic thromboembolism. Strokes related to AF are associated with higher mortality, greater disability, longer hospital stays, and lower chance of being discharged home. The present review will focus on the current status of detecting NVAF and stroke prevention when there is AF. The CHA2DS2-VASc risk stratification scheme is discussed for the identification of patients who are at risk for thromboembolic stroke related to NVAF. Patient with a CHA2DS2-VASc score of 2 or greater are candidates for warfarin or a novel oral anticoagulant, irrespective of whether the strategy is for rate or rhythm control. Finally, guidelines and landmark clinical trials in NVAF patients with primary or secondary stroke prevention are discussed. PMID:27263867

  12. Discrepancies between Patients’ Preferences and Educational Programs on Oral Anticoagulant Therapy: A Survey in Community Pharmacies and Hospital Consultations

    PubMed Central

    Macquart de Terline, Diane; Hejblum, Gilles; Fernandez, Christine; Cohen, Ariel; Antignac, Marie

    2016-01-01

    Background Oral anticoagulation therapy is increasingly used for the prevention and treatment of thromboembolic complications in various clinical situations. Nowadays, education programs for patients treated with anticoagulants constitute an integrated component of their management. However, such programs are usually based on the healthcare providers’ perceptions of what patients should know, rather than on patients’ preferences. Objective To investigate patients’ viewpoints on educational needs and preferred modalities of information delivery. Methods We conducted an observational study based on a self-administered questionnaire. To explore several profiles of patients, the study was designed for enrolling patients in two settings: during outpatient consultations in a cardiology department (Saint Antoine Hospital, Paris, France) and in community pharmacies throughout France. Results Of the 371 patients who completed the questionnaire, 187 (50.4%) were recruited during an outpatient consultation and 184 (49.6%) were recruited in community pharmacies. 84.1% of patients were receiving a vitamin K antagonist and 15.6% a direct oral anticoagulant. Patients ranked 16 of 21 (76.2%) questionnaire items on information about their treatment as important or essential; information on adverse effects of treatment was the highest ranked domain (mean score 2.38, 95% CI 2.30–2.46). Pharmacists (1.69, 1.58–1.80), nurses (1.05, 0.95–1.16), and patient associations (0.36, 0.29–0.44), along with group sessions (0.85, 0.75–0.95), the internet (0.77, 0.67–0.88), and delivery of material at the patient’s home (1.26, 1.14–1.38), were ranked poorly in terms of delivering educational material. Conclusion This study revealed substantial discrepancies between patient preferences and current educational programs. These findings should be useful for tailoring future educational programs that are better adapted to patients, with a potential associated enhancement of their

  13. Supporting patients to self-monitor their oral anticoagulation therapy: recommendations based on a qualitative study of patients’ experiences

    PubMed Central

    Tompson, Alice; Heneghan, Carl; Fitzmaurice, David; Sutton, Stephen; Harrison, Sian; Ward, Alison

    2015-01-01

    Background Clinical trials suggest that oral anticoagulation therapy (OAT) self-monitoring is safe and effective, however little is known about the patient experience of this process. There is a lack of understanding about how best to train and support patients embarking on OAT self-monitoring. Aim To collect in-depth information about patients’ experiences of OAT self-monitoring outside of clinical trial conditions and to produce a set of recommendations on how best to support such patients. Design and setting Semi-structured qualitative interviews with patients who self-monitor and live in England. Method In total, 26 of the 267 (9.7%) who participated in the Cohort study of Anticoagulation Self-Monitoring (CASM) and were still self-monitoring after 12 months’ follow-up were interviewed. Topics discussed included experiences of OAT self-monitoring, healthcare support, training, and decision making. Framework analysis was used. Results Following initial problems using the monitoring device, interviewees described a mostly positive experience. Although less effort was expended attending monitoring appointments with health professionals, effort was required to conduct self-monitoring tests and to interpret and act on the results. Desire to self-manage was variable, especially when dosing advice systems worked promptly and reliably. Interviewees overcame patchy healthcare system knowledge and support of self-monitoring by educating themselves. Family and friends provided support with learning to use the monitor and managing OAT dosage adjustments. Conclusion Better, more-consistent training and health-service support would have alleviated a number of problems encountered by these patients who were self-monitoring. This training and support will become even more important if self-monitoring becomes more accessible to the general population of people on OAT. PMID:26077266

  14. Maternal malaria induces a procoagulant and antifibrinolytic state that is embryotoxic but responsive to anticoagulant therapy.

    PubMed

    Avery, John W; Smith, Geoffrey M; Owino, Simon O; Sarr, Demba; Nagy, Tamas; Mwalimu, Stephen; Matthias, James; Kelly, Lauren F; Poovassery, Jayakumar S; Middii, Joab D; Abramowsky, Carlos; Moore, Julie M

    2012-01-01

    Low birth weight and fetal loss are commonly attributed to malaria in endemic areas, but the cellular and molecular mechanisms that underlie these poor birth outcomes are incompletely understood. Increasing evidence suggests that dysregulated hemostasis is important in malaria pathogenesis, but its role in placental malaria (PM), characterized by intervillous sequestration of Plasmodium falciparum, proinflammatory responses, and excessive fibrin deposition is not known. To address this question, markers of coagulation and fibrinolysis were assessed in placentae from malaria-exposed primigravid women. PM was associated with significantly elevated placental monocyte and proinflammatory marker levels, enhanced perivillous fibrin deposition, and increased markers of activated coagulation and suppressed fibrinolysis in placental plasma. Submicroscopic PM was not proinflammatory but tended to be procoagulant and antifibrinolytic. Birth weight trended downward in association with placental parasitemia and high fibrin score. To directly assess the importance of coagulation in malaria-induced compromise of pregnancy, Plasmodium chabaudi AS-infected pregnant C57BL/6 mice were treated with the anticoagulant, low molecular weight heparin. Treatment rescued pregnancy at midgestation, with substantially decreased rates of active abortion and reduced placental and embryonic hemorrhage and necrosis relative to untreated animals. Together, the results suggest that dysregulated hemostasis may represent a novel therapeutic target in malaria-compromised pregnancies. PMID:22347435

  15. [GOOD PLANNING PRACTICE IN PRECLINICAL AND CLINICAL STUDIES OF UNFRACTIONATED AND FRACTIONATED HEPARINS IN RUSSIA AS THE BASIS OF SAFE AND EFFECTIVE ANTICOAGULATION THERAPY].

    PubMed

    Gavrishina, E V; Dobrovolskii, A V; Niyazov, R R; Romodanovskii, D P; Vasil'ev, A N

    2015-01-01

    General principles of appropriate strategies for preclinical and clinical development of unfractionated and low-molecular-weight heparins and demonstration of their biosimilarity to corresponding reference medicinal products are provided. Demonstration of the biosimilarity of heparin-containing medicinal products constitutes the basis for their efficacy and safety during anticoagulation therapy. The main quality, safety, and efficacy characteristics of heparin products are described and the extent of non-clinical and clinical investigations necessary prior to drug marketing authorization are considered. PMID:27017700

  16. Anticoagulant rodenticides.

    PubMed

    Watt, Barbara E; Proudfoot, Alex T; Bradberry, Sally M; Vale, J Allister

    2005-01-01

    Anticoagulant pesticides are used widely in agricultural and urban rodent control. The emergence of warfarin-resistant strains of rats led to the introduction of a new group of anticoagulant rodenticides variously referred to as 'superwarfarins', 'single dose' or 'long-acting'. This group includes the second generation 4-hydroxycoumarins brodifacoum, bromadiolone, difenacoum, flocoumafen and the indanedione derivatives chlorophacinone and diphacinone. Most cases of anticoagulant rodenticide exposure involve young children and, as a consequence, the amounts ingested are almost invariably small. In contrast, intentional ingestion of large quantities of long-acting anticoagulant rodenticides may cause anticoagulation for several weeks or months. Occupational exposure has also been reported. Anticoagulant rodenticides inhibit vitamin K(1)-2,3 epoxide reductase and thus the synthesis of vitamin K and subsequently clotting factors II, VII, IX and X. The greater potency and duration of action of long-acting anticoagulant rodenticides is attributed to their: (i) greater affinity for vitamin K(1)-2,3-epoxide reductase; (ii) ability to disrupt the vitamin K(1)-epoxide cycle at more than one point; (iii) hepatic accumulation; and (iv) unusually long biological half-lives due to high lipid solubility and enterohepatic circulation. Substantial ingestion produces epistaxis, gingival bleeding, widespread bruising, haematomas, haematuria with flank pain, menorrhagia, gastrointestinal bleeding, rectal bleeding and haemorrhage into any internal organ; anaemia may result. Spontaneous haemoperitoneum has been described. Severe blood loss may result in hypovolaemic shock, coma and death. The first clinical signs of bleeding may be delayed and patients may remain anticoagulated for several days (warfarin) or days, weeks or months (long-acting anticoagulants) after ingestion of large amounts. There are now sufficient data in young children exposed to anticoagulant rodenticides to

  17. Preference for oral anticoagulation therapy for patients with atrial fibrillation in Europe in different clinical situations: results of the European Heart Rhythm Association Survey.

    PubMed

    Larsen, Torben Bjerregaard; Potpara, Tatjana; Dagres, Nikolaos; Proclemer, Alessandro; Sciarrafia, Elena; Blomström-Lundqvist, Carina

    2015-05-01

    The purpose of this European Heart Rhythm Association Survey was to assess the clinical practice in relation to the use of oral anticoagulation therapy for patients with atrial fibrillation (AF) in Europe. Of special interest were patients undergoing percutaneous coronary intervention (PCI), cardioversion procedures, catheter ablation, surgery, and those suffering from anticoagulation-related bleeding. Of 38 responding centres, non-vitamin K antagonist oral anticoagulants (NOACs) were used for stroke prophylaxis and were preferred (33.3%) or considered equal (48.5%) to vitamin K antagonists (VKAs). Only 3% did not use NOACs at all. There were some practice differences regarding the use of NOACs in combination with dual antiplatelet therapy in AF patients undergoing PCI, and only 12% preferred using NOACs in this setting. Bare metal stents were preferred rather than drug-eluting stents in AF patients at high bleeding risk. There were clear practice differences between centres regarding the use of triple therapy. Most of the major bleeding events would be handled using symptomatic and supportive measures (e.g. mechanical compression, fluid replacement, blood transfusion, prothrombin complex concentrate, or recombinant Factor VIIa). More than 80% of the centres offer either VKA or NOAC for at least 3 weeks before and after cardioversion and 70% offer either VKA or NOAC before and after AF catheter ablation. Patients treated with an NOAC were routinely re-assed in most centres. PMID:25926476

  18. Novel oral anticoagulants.

    PubMed

    Reiffel, James A

    2014-04-01

    Warfarin has a proven record as an oral anticoagulant; almost every study, however, has found that it is not prescribed for 40-60% of patients who are eligible and should receive it, and of those who do receive it, serum warfarin levels only achieved a time in therapeutic range (TTR) equal to INR 2-3 about 55-60% of the time (online video available at: http://education.amjmed.com/video.php?event_id=445&stage_id=5&vcs=1). This means that only about 1 in 4 patients are adequately anticoagulated with warfarin, and thus there is a large unmet need for achieving better anticoagulation in these patients. Although physicians have sometimes tried to use antiplatelet therapy (aspirin, plus or minus clopidogrel) for anticoagulation, this may result in as much as a doubling of the risk of thromboembolic events. Recently 2 new classes of oral anticoagulant agents have appeared: direct thrombin inhibitors (DTIs) and factor Xa inhibitors. This review sequentially examines the recent clinical trial evidence for the 3 approved NOACs in the 2 classes, highlighting that all 3 share a class effect of being noninferior to warfarin for reducing risk of stroke and systemic embolization and reducing risk of bleeding, with a relative risk of mortality consistently reduced by 10% per year. In addition, all of the NOACs have a significantly lower risk of intracranial/intracerebral bleeding than warfarin, an important clinical consideration, since that is the most feared bleeding risk and may be sufficient reason to consider switching patients from warfarin to a NOAC, even if they seem to be doing well on warfarin. Finally in addition to reviewing the overall benefits of these NOACs over traditional therapy, the clinical application differences between the classes and between the agents are reviewed. PMID:24655744

  19. [Anticoagulation in atrial fibrillation].

    PubMed

    Schwarz, M; Bode, Ch

    2008-10-01

    In this overview the actual guideline-recommendations for anticoagulation in atrial fibrillation and the problems of the currently available therapy are discussed. Furthermore an outlook over future developments in this field is given. Effective anticoagulation can prohibit thrombembolic events and is thus essential for the prognosis of patients suffering from atrial fibrillation. Until now vitamin-K-antagonists (VKAs) and acetylsalicylic acid (ASA) are available for oral anticoagulation in these patients. VKAs demonstrate a satisfying efficiency combined with rather high bleeding hazard. ASA on the other hand allows only moderate risk reduction with minimal side effects. Thus the guidelines recommend anticoagulation tailored to the individual risk, which can be evaluated by the CHADS2-Score. New therapeutic strategies, like the factor Xa inhibitor rivaroxaban or the factor II inhibitor dabigatran, are actually evaluated in phase III studies. These drugs bear the hope of higher efficiency combined with improved safety and much more comfortable use in the daily practice (e. g. no need for INR measurement, no dose adaptation). PMID:18836647

  20. Anticoagulation in atrial fibrillation

    PubMed Central

    Piccini, Jonathan P

    2014-01-01

    Atrial fibrillation increases the risk of stroke, which is a leading cause of death and disability worldwide. The use of oral anticoagulation in patients with atrial fibrillation at moderate or high risk of stroke, estimated by established criteria, improves outcomes. However, to ensure that the benefits exceed the risks of bleeding, appropriate patient selection is essential. Vitamin K antagonism has been the mainstay of treatment; however, newer drugs with novel mechanisms are also available. These novel oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) obviate many of warfarin’s shortcomings, and they have demonstrated safety and efficacy in large randomized trials of patients with non-valvular atrial fibrillation. However, the management of patients taking warfarin or novel agents remains a clinical challenge. There are several important considerations when selecting anticoagulant therapy for patients with atrial fibrillation. This review will discuss the rationale for anticoagulation in patients with atrial fibrillation; risk stratification for treatment; available agents; the appropriate implementation of these agents; and additional, specific clinical considerations for treatment. PMID:24733535

  1. Anticoagulation in atrial fibrillation.

    PubMed

    Steinberg, Benjamin A; Piccini, Jonathan P

    2014-01-01

    Atrial fibrillation increases the risk of stroke, which is a leading cause of death and disability worldwide. The use of oral anticoagulation in patients with atrial fibrillation at moderate or high risk of stroke, estimated by established criteria, improves outcomes. However, to ensure that the benefits exceed the risks of bleeding, appropriate patient selection is essential. Vitamin K antagonism has been the mainstay of treatment; however, newer drugs with novel mechanisms are also available. These novel oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) obviate many of warfarin's shortcomings, and they have demonstrated safety and efficacy in large randomized trials of patients with non-valvular atrial fibrillation. However, the management of patients taking warfarin or novel agents remains a clinical challenge. There are several important considerations when selecting anticoagulant therapy for patients with atrial fibrillation. This review will discuss the rationale for anticoagulation in patients with atrial fibrillation; risk stratification for treatment; available agents; the appropriate implementation of these agents; and additional, specific clinical considerations for treatment. PMID:24733535

  2. Outcomes and predictors of very stable INR control during chronic anticoagulation therapy.

    PubMed

    Witt, Daniel M; Delate, Thomas; Clark, Nathan P; Martell, Chad; Tran, Thu; Crowther, Mark A; Garcia, David A; Ageno, Walter; Hylek, Elaine M

    2009-07-30

    For patients on warfarin therapy, an international normalized ratio (INR) recall interval not exceeding 4 weeks has traditionally been recommended. Less frequent INR monitoring may be feasible in stable patients. We sought to identify patients with stable INRs (defined as having INR values exclusively within the INR range) and comparator patients (defined as at least one INR outside the INR range) in a retrospective, longitudinal cohort study. Occurrences of thromboembolism, bleeding, and death were compared between groups. Multivariate logistic regression models were used to identify independent predictors of stable INR control. There were 2504 stable and 3569 comparator patients. The combined rates of bleeding and thromboembolism were significantly lower in stable patients. Independent predictors of stable INR control were age older than 70 years and the absence of comorbid heart failure and diabetes. Stable patients were significantly less likely to have target INR of 3.0 or higher or chronic diseases. We hypothesize that many patients demonstrating stable INR control could be safely treated with INR recall intervals greater than the traditional 4 weeks. PMID:19439733

  3. Non-Vitamin K Antagonist Oral Anticoagulants and Antiplatelet Therapy for Stroke Prevention in Patients With Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Kumar, Shashi; Danik, Stephan B; Altman, Robert K; Barrett, Conor D; Lip, Gregory Y H; Chatterjee, Saurav; Roubin, Gary S; Natale, Andrea; Danik, Jacqueline S

    2016-01-01

    Non-vitamin K antagonist oral anticoagulants (NOACs) are frequently used to prevent stroke in patients with atrial fibrillation. These patients are often also on aspirin or other antiplatelet agents. It is possible that treatment with both NOACs and aspirin or other antiplatelet drug may be effective in decreasing stroke, but data are sparse regarding the efficacy and safety of using both agents for stroke prevention. To address these issues, data were pooled from the 4 recent randomized, controlled trials of NOACs: apixaban, rivaroxaban, dabigatran, and edoxaban, which included 42,411 patients; 14,148 (33.4%) were also on aspirin or other antiplatelet drug. The number of thromboembolic events among participants on NOAC and aspirin/antiplatelet was compared with the number of events in patients on NOAC alone. Bleeding rates were also compared between those on NOAC + aspirin/antiplatelet and on NOAC alone. These results were compared with thromboembolic and bleeding events in the warfarin + aspirin/antiplatelet versus warfarin alone. No greater risk for thromboembolism was seen in patients on NOACs compared with patients on both NOACs and aspirin/antiplatelet drug. In this nonrandomized comparison, there was initially a signal toward higher thromboembolic rates among NOAC users also on aspirin/antiplatelet drugs (relative risk, 1.16; 95% confidence intervals, 1.05, 1.29) when compared with NOAC alone. This likely reflected the higher CHADS2 scores of those on aspirin/antiplatelet drugs. When the analysis was limited to studies that included aspirin rather than other antiplatelet drugs, no difference was seen for thromboembolic rates comparing dual therapy to NOAC alone (relative risk, 1.02; 95% confidence intervals, 0.90, 1.15). Higher rates of bleeding were seen with aspirin/antiplatelet drug in conjunction with NOAC. In this meta-analysis and nonrandomized comparison of aspirin/antiplatelet users and nonusers also on anticoagulation, there was no additional

  4. Use of Percutaneous Aspiration Thrombectomy vs. Anticoagulation Therapy to Treat Acute Iliofemoral Venous Thrombosis: 1-year Follow-up Results of a Randomised, Clinical Trial

    SciTech Connect

    Cakir, Volkan; Gulcu, Aytac; Akay, Emrah; Capar, Ahmet E.; Gencpinar, Tugra; Kucuk, Banu; Karabay, Ozalp; Goktay, A. Yigit

    2014-08-15

    PurposeThe purpose of this study was to compare the efficacy of percutaneous aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with anticoagulation therapy alone, for the treatment of acute proximal lower extremity deep vein thrombosis.MethodsIn this randomised, prospective study, 42 patients with acute proximal iliofemoral deep vein thrombosis documented via Doppler ultrasound examination, were separated into an interventional treatment group (16 males, 5 females, average age 51 years) and a medical treatment group (13 males, 8 females, average age 59 years). In the interventional group, PAT with large-lumen 9-F diameter catheterisation was applied, after initiation of standard anticoagulant therapy. Balloon angioplasty (n 19) and stent implementation (n: 14) were used to treat patients with residual stenosis (>50 %) after PAT. Prophylactic IVC filters were placed in two patients. The thrombus clearance status of the venous system was evaluated by venography. In both the medical and interventional groups, venous patency rates and clinical symptom scores were evaluated at months 1, 3, and 12 after treatment.ResultsDeep venous systems became totally cleared of thrombi in 12 patients treated with PAT. The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional and medical treatment groups, respectively. A statistically significant improvement was observed in clinical symptom scores of the interventional group (PAT) with or without stenting (4.23 ± 0.51 before treatment; 0.81 ± 0.92 at month 12) compared with the medical treatment group (4.00 ± 0.63 before treatment; 2.43 ± 0.67 at month 12). During follow-up, four patients in the medical treatment and one in the interventional group developed pulmonary embolisms.ConclusionsFor treatment of acute deep vein thrombosis, PAT with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical

  5. Oral anticoagulant therapy for stroke prevention in patients with atrial fibrillation undergoing ablation: results from the First European Snapshot Survey on Procedural Routines for Atrial Fibrillation Ablation (ESS-PRAFA).

    PubMed

    Potpara, Tatjana S; Larsen, Torben B; Deharo, Jean Claude; Rossvoll, Ole; Dagres, Nikolaos; Todd, Derick; Pison, Laurent; Proclemer, Alessandro; Purefellner, Helmut; Blomström-Lundqvist, Carina

    2015-06-01

    The European Snapshot Survey on Procedural Routines in Atrial Fibrillation Ablation (ESS-PRAFA) is a prospective, multicentre snapshot survey of patients undergoing atrial fibrillation (AF) ablation, conducted to collect patient-based data on current clinical practices in AF ablation in context of the latest AF Guidelines and contemporary oral anticoagulant therapies. The EP Research Network Centres were asked to prospectively enrol consecutive patients during a 6-week period (September/October 2014). Data were collected via the web-based case report form. We present the results pertinent to the use of antithrombotic therapies. Thirteen countries prospectively enrolled 455 eligible consecutive patients [mean age 59 ± 10.8 years, 131 (28.8%) females]. The mean CHA2DS2-VASc score was 1.12 ± 1.06 [137 patients (30.1%) had a score of ≥2]. Before ablation, 443 patients (97.4%) were on anticoagulant therapy [143 (31.4%) on non-vitamin K antagonist oral anticoagulants (NOACs) and 264 (58.0%) on vitamin K antagonists (VKAs)]. Of the latter, 79.7% underwent ablation without VKA interruption, whilst a variety of strategies were used in patients taking NOAC. After ablation, most patients (89.3%) continued the same anticoagulant as before, and 2 (0.4%) were not prescribed any anticoagulation. At discharge, 280 patients (62.2%) were advised oral anticoagulation for a limited period of mean 3.8 ± 2.2 months. On multivariate analysis, CHA2DS2-VASc, AF duration, prior VKA use, and estimated AF ablation success were significantly associated with the decision on short-term anticoagulation. Our results show the increasing use of NOAC in patients undergoing AF ablation and emphasize the need for more information to guide the periprocedural use of both NOACs and VKAs in real-world setting. PMID:26023177

  6. Attitudes and Preferences on the Use of Mobile Health Technology and Health Games for Self-Management: Interviews With Older Adults on Anticoagulation Therapy

    PubMed Central

    Nguyen, Annie Lu; Berg, Jill; Amin, Alpesh; Bachman, Mark; Guo, Yuqing; Evangelista, Lorraine

    2014-01-01

    Background Older adults are at substantial risk for cardiovascular disorders that may require anticoagulation therapy. Those on warfarin therapy report dissatisfaction and reduced quality of life (QOL) resulting from the treatment. Advances in the area of mobile health (mHealth) technology have resulted in the design and development of new patient-centric models for the provision of personalized health care services to improve care delivery. However, there is a paucity of research examining the effectiveness of mHealth tools on knowledge, attitudes, and patient satisfaction with treatment, as well as self-management, adherence to therapy, and QOL in older adults with chronic illness conditions requiring long-term warfarin therapy. Objective The objective of the study was to explore the attitudes and preferences of older adults on warfarin therapy regarding the use of mHealth technology and health games to gain skills for self-management. Methods We conducted group and individual interviews with patients (60 years or older) on warfarin therapy at two anticoagulation clinics affiliated with an academic medical center. We held 4 group and 2 individual interviews, resulting in 11 patient participants and 2 family caregiver participants. We used structured questions on three topic areas including medication self-management strategies, mHealth technology use, and health games for exercise. We demonstrated some commercial health apps related to medication management, vitamin K content of food, and a videogame for balance exercise. Discussions were audiotaped and transcribed verbatim. Common themes were drawn using content analysis. Results The participants reported awareness of the importance of staying on schedule with warfarin therapy. They also acknowledged that negative experiences of friends or family members who were taking warfarin influenced their desire to keep on schedule with warfarin therapy. In addition, the participants expressed that the use of m

  7. Pharmacology of anticoagulants used in the treatment of venous thromboembolism.

    PubMed

    Nutescu, Edith A; Burnett, Allison; Fanikos, John; Spinler, Sarah; Wittkowsky, Ann

    2016-01-01

    Anticoagulant drugs are the foundation of therapy for patients with VTE. While effective therapeutic agents, anticoagulants can also result in hemorrhage and other side effects. Thus, anticoagulant therapy selection should be guided by the risks, benefits and pharmacologic characteristics of each agent for each patient. Safe use of anticoagulants requires not only an in-depth knowledge of their pharmacologic properties but also a comprehensive approach to patient management and education. This paper will summarize the key pharmacologic properties of the anticoagulant agents used in the treatment of patients with VTE. PMID:26780737

  8. New anticoagulants: focus on venous thromboembolism.

    PubMed

    Gómez-Outes, Antonio; Lecumberri, Ramón; Pozo, Carmen; Rocha, Eduardo

    2009-07-01

    Anticoagulation is recommended for prophylaxis and treatment of venous thromboembolism (VTE) (deep vein thrombosis and pulmonary embolism) and/or arterial thromboembolism. The therapeutic arsenal of anticoagulants available to clinicians is mainly composed by unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), fondaparinux and oral vitamin K antagonists (VKA) (i.e. warfarin and acenocumarol). These anticoagulants are effective, but they require parenteral administration (UFH, LMWH, fondaparinux) and/or frequent anticoagulant monitoring (intravenous UFH, oral VKA). Novel anticoagulants in clinical testing include orally active direct factor II inhibitors [dabigatran etexilate (BIBR 1048), AZD0837)], parenteral direct factor II inhibitors (flovagatran sodium), orally active direct factor X inhibitors [rivaroxaban (BAY 59-7939), apixaban, betrixaban, YM150, DU-176b, LY-517717, GW813893, TAK-442, PD 0348292] and new parenteral FXa inhibitors [idraparinux, idrabiotaparinux (biotinilated idraparinux; SSR 126517), ultra-low-molecular-weight heparins (ULMWH: AVE5026, RO-14)]. These new compounds have the potential to complement heparins and fondaparinux for short-term anticoagulation and/or to replace VKA for long-term anticoagulation in most patients. Dabigatran and rivaroxaban have been the firsts of the new oral anticoagulants to be licensed for the prevention of VTE after hip and knee replacement surgery. In the present review, we discuss the pharmacology of new anticoagulants, the key points necessary for interpreting the results of studies on VTE prophylaxis and treatment, the results of clinical trials testing these new compounds and their potential advantages and drawbacks over existing therapies. PMID:19601856

  9. XALIA: rationale and design of a non-interventional study of rivaroxaban compared with standard therapy for initial and long-term anticoagulation in deep vein thrombosis

    PubMed Central

    2014-01-01

    Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism, poses a substantial clinical risk, and the incidence of these thrombotic-related diseases remains high. Anticoagulation aims to prevent thrombus extension and reduce the risk of recurrent events, particularly fatal pulmonary embolism. In EINSTEIN DVT, rivaroxaban was non-inferior to enoxaparin/vitamin K antagonists for the reduction of recurrent VTE, with a similar safety profile and a net clinical benefit. EINSTEIN EXT investigated patients receiving long-term treatment in whom there was no clear decision about continuing or stopping anticoagulation; rivaroxaban was superior to placebo in the reduction of recurrent VTE, showing an acceptable benefit–risk balance. Rivaroxaban has the potential to replace standard therapy, usually parenteral low molecular weight heparin overlapping with and followed by a vitamin K antagonist, for the treatment of acute symptomatic DVT and the secondary prevention of VTE. As the use of rivaroxaban for DVT treatment increases in clinical practice, a fundamental understanding of its clinical benefits in everyday patient care is essential. XALIA (XArelto for Long-term and Initial Anticoagulation in venous thromboembolism) is a multicentre, prospective, non-interventional, observational study investigating the effectiveness and safety of a single-drug approach with rivaroxaban compared with standard therapy in patients with DVT. The study cohort will include approximately 4800 patients (≥18 years old) with objectively confirmed acute DVT who will be treated for a period of ≥3 months. The primary outcomes will be the incidence of treatment-emergent adverse events (primarily major bleeding), symptomatic recurrent venous thromboembolic events and all-cause mortality. Secondary outcomes include: major cardiovascular events; patient-reported treatment satisfaction and adherence; healthcare resource utilization; reasons for drug switching or

  10. [Anticoagulants after intracerebral haemorrhage in frail elderly].

    PubMed

    Olde Rikkert, Marcel; Claassen, Jurgen

    2015-01-01

    Restarting anticoagulants in frail older patients who have had an intracerebral haemorrhage as an adverse reaction to anticoagulant therapy is a major dilemma, and one which is not specifically addressed in the state-of-the-art paper on restarting anticoagulants elsewhere in this issue. Frail older persons have the highest risk of recurrent bleeding, but, in theory, also have the most benefit from anticoagulants due to the high absolute risk for ischemic events in atrial fibrillation, which is the major indication. However, frail older persons are largely excluded from trials with anticoagulants, which makes it impossible to solve this dilemma in an evidence-based way. Therefore, we argue that sound decision making cannot only be based on neurological or cardiological expertise, as proposed by others, but should include an overall comprehensive geriatric assessment, and, most importantly, patients and caregivers should be included in shared goal setting and shared decision making. PMID:25873225

  11. Engaging with quality improvement in anticoagulation management.

    PubMed

    Barnes, Geoffrey D; Kline-Rogers, Eva

    2015-04-01

    Anticoagulants are highly effective at preventing thrombosis across a variety of clinical indications. However, their use can also lead to devastating effects, including major bleeding and death. Anticoagulation providers strive to balance the benefits of anticoagulant therapy with the risks of major bleeding. A measure of quality care can be used to assess the strengths and potential weaknesses in any system of coordinated care delivery. Quality measures in anticoagulation include patient-centered outcomes (e.g. major bleeding, time in the therapeutic range) and provider- or process-focused outcomes (e.g. compliance with guideline recommendations and response times to out-of-range laboratory values). Engaging in quality improvement activities allows anticoagulation providers to assess their own performance and identify areas for targeted interventions. This review summarizes the justification for engaging in quality improvement for anticoagulation management and describes a number of example programs. Interventions benefiting the management of both warfarin and the direct oral anticoagulants are included. The review also details potential quality measures and resources for any anticoagulation provider looking to begin a quality improvement process. PMID:25772116

  12. Anticoagulant modulation of inflammation in severe sepsis

    PubMed Central

    Allen, Karen S; Sawheny, Eva; Kinasewitz, Gary T

    2015-01-01

    Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review examines the interaction between the inflammatory and coagulation cascades, as well as the role of endogenous anticoagulants in regulating this interaction and dampening the activity of both pathways. Clinical trials attempting to improve outcomes in patients with severe sepsis by inhibiting thrombin generation with heparin and or endogenous anticoagulants are reviewed. In general, these trials have failed to demonstrate that anticoagulant therapy is associated with improvement in mortality or morbidity. While it is possible that selective patients who are severely ill with a high expected mortality may be shown to benefit from such therapy, at the present time none of these anticoagulants are neither approved nor can they be recommended for the treatment of sepsis. PMID:25938026

  13. Percutaneous tracheostomy in patients on anticoagulants

    PubMed Central

    Pasin, Laura; Frati, Elena; Cabrini, Luca; Giovanni, Landoni; Nardelli, Pasquale; Bove, Tiziana; Calabrò, Maria Grazia; Scandroglio, Anna Mara; Pappalardo, Federico; Zangrillo, Alberto

    2015-01-01

    Aims: To determine if percutaneous tracheostomy is safe in critically ill patients treated with anticoagulant therapies. Settings and Design: Single-center retrospective study including all the patients who underwent percutaneous dilatational tracheostomy (PDT) placement over a 1-year period in a 14-bed, cardiothoracic and vascular Intensive Care Unit (ICU). Materials and Methods: Patients demographics and characteristics, anticoagulant and antiplatelet therapies, coagulation profile, performed technique and use of bronchoscopic guidance were retrieved. Results: Thirty-six patients (2.7% of the overall ICU population) underwent PDT over the study period. Twenty-six (72%) patients were on anticoagulation therapy, 1 patient was on antiplatelet therapy and 2 further patients received prophylactic doses of low molecular weight heparin. Only 4 patients had normal coagulation profile and were not receiving anticoagulant or antiplatelet therapies. Overall, bleeding of any severity complicated 19% of PDT. No procedure-related deaths occurred. Conclusions: PDT was proved to be safe even in critically ill-patients treated with anticoagulant therapies. Larger prospective studies are needed to confirm our findings. PMID:26139737

  14. Characteristics affecting oral anticoagulant therapy choice among patients with non-valvular atrial fibrillation: a retrospective claims analysis

    PubMed Central

    2014-01-01

    Background Dabigatran is one of the three newer oral anticoagulants (OACs) recently approved in the United States for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. The objective of this study was to identify patient, healthcare provider, and health plan factors associated with dabigatran versus warfarin use among NVAF patients. Methods Administrative claims data from patients with ≥2 NVAF medical claims in the HealthCore Integrated Research Database between 10/1/2009 and 10/31/2011 were analyzed. During the study intake period (10/1/2010 - 10/31/2011), dabigatran patients had ≥2 dabigatran prescriptions, warfarin patients had ≥2 warfarin and no dabigatran prescriptions, and the first oral anticoagulant (OAC) prescription date was the index date. Continuous enrollment for 12 months preceding (“pre-index”) and ≥ 6 months following the index date was required. Patients without pre-index warfarin use were assigned to the ‘OAC-naïve’ subgroup. Separate analyses were performed for ‘all-patient’ and ‘OAC-naïve’ cohorts. Multivariable logistic regression (LR) identified factors associated with dabigatran versus warfarin use. Results Of 20,320 patients (3,019 dabigatran and 17,301 warfarin) who met study criteria, 27% of dabigatran and 13% of warfarin patients were OAC-naïve. Among all-patients, dabigatran patients were younger (mean 67 versus 73 years, p < 0.001), predominantly male (71% versus 61%, p < 0.001), and more frequently had a cardiologist prescriber (51% versus 30%, p < 0.001) than warfarin patients. Warfarin patients had higher pre-index Elixhauser Comorbidity Index (mean: 4.3 versus 4.0, p < 0.001) and higher ATRIA bleeding risk score (mean: 3.0 versus 2.3, p < 0.001). LR results were generally consistent between all- and OAC-naïve patients. Among OAC-naïve patients, strongest factors associated with dabigatran use were prescriber specialty (OR = 3.59, 95% CI 2.68-4.81 for

  15. New anticoagulants for treatment of venous thromboembolism.

    PubMed

    Gross, Peter L; Weitz, Jeffrey I

    2008-03-01

    Anticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). Such treatment is divided into 2 stages: Rapid initial anticoagulation is given to minimize the risk of thrombus extension and fatal pulmonary embolism, whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby reducing the risk of postphlebitic syndrome. With currently available drugs, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists, such as warfarin. Emerging anticoagulants have the potential to streamline VTE treatment. These agents include idraparinux, a long-acting synthetic pentasaccharide that is given subcutaneously on a once-weekly basis, and new oral anticoagulants that target thrombin or factor Xa. This article (1) reviews the pharmacology of these agents, (2) outlines their potential strengths and weaknesses, (3) describes the results of clinical trials with these new drugs, and (4) identifies the evolving role of new anticoagulants in the management of VTE. PMID:18296593

  16. Novel oral anticoagulants in the management of coronary artery disease.

    PubMed

    McMahon, Sean R; Brummel-Ziedins, Kathleen; Schneider, David J

    2016-08-01

    Despite advances in interventional and pharmacologic therapy, survivors of myocardial infarction remain at an increased risk of subsequent cardiovascular events. Initial pharmacological management includes both platelet inhibition and parenteral anticoagulation, whereas long-term pharmacological therapy relies on antiplatelet therapy for prevention of thrombotic complications. Biomarkers showing ongoing thrombin generation after acute coronary syndromes suggest that anticoagulants may provide additional benefit in reducing cardiovascular events. We review the pharmacokinetics of novel anticoagulants, clinical trial results, the role of monitoring, and future directions for the use of novel oral anticoagulants in the treatment of coronary artery disease. Clinical trials have shown that long-term use of oral anticoagulants decreases the risk of cardiovascular events, but they do so at a cost of an increased risk of bleeding. Future studies will need to identify optimal treatment combinations for selected patients and conditions that address both the appropriate combination of therapy and the appropriate dosage of each agent when used in combination. PMID:27228186

  17. Practicability of patient self-testing of oral anticoagulant therapy by the international normalized ratio (INR) using a portable whole blood monitor. A pilot investigation.

    PubMed

    Hasenkam, J M; Knudsen, L; Kimose, H H; Grønnesby, H; Attermann, J; Andersen, N T; Pilegaard, H K

    1997-01-01

    The prophylactic efficacy of long-term oral anticoagulant treatment (OAT) has been demonstrated in a number of clinical conditions with increased tendency to thromboembolism, and the number of individuals subjected to OAT in the industrialised world has increased substantially in recent years. Since this therapy requires considerable resources from both the health care system and the patients, the feasibility of patients' self-monitoring and self-management of OAT has been investigated (1,2,3). The anticipated advantages of this approach include improved convenience and compliance for the patient, who may increase his apprehension for managing the treatment. In addition, self-testing allows for more frequent control compared to the conventional out-patient approach. Importantly, a prerequisite for conceiving a safe and operational concept for patient self-management (PSM) is the availability of a portable INR monitoring system with an accuracy, precision, reproducibility, and long-term reliability comparable to standard coagulometric equipment. The purpose of the present study was to evaluate the feasibility of a commercially available INR-monitor. CoaguChek, for patient self-testing, through a step-wise investigation of the performance characteristics of the equipment in the laboratory, in command of the patient, and during self-testing and self-adjustment of treatment at home. Laboratory INR values were used as reference. PMID:8983128

  18. Optical profiling of anticoagulation status (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Tshikudi, Diane M.; Tripathi, Markandey M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.

    2016-02-01

    Defective blood coagulation resulting from excessive procoagulant activity often leads to thrombotic disorders such as stroke and myocardial infarction. A variety of oral and injectable anticoagulant drugs are prescribed to prevent or treat life-threatening thrombosis. However, due to bleeding complications often associated with anticoagulant treatment, routine monitoring and accurate dosing of anticoagulant therapy is imperative. We have developed Optical thromboelastography (OTEG), a non-contact approach that utilizes a drop of whole blood to measure blood coagulation status in patients. Here, we demonstrate the capability of OTEG for rapidly monitoring anticoagulation in whole blood samples. OTEG monitors coagulation status by assessing changes in blood viscosity from temporal intensity fluctuations of laser speckle patterns during clotting. In OTEG a blood drop is illuminated with coherent light and the blood viscosity is measured from the speckle intensity autocorrelation curve, g2 (t). The metrics, clotting time (R+k), clot progression (angle) and maximum clot stiffness (MA) are then extracted. The aim of the current study was to evaluate the accuracy of OTEG in assessing anticoagulation status of common anticoagulants including heparin, argatroban and rivaroxaban status. A dose-dependent prolongation of R+k was observed in anticoagulated blood, which closely corresponded with standard-reference Thromboelastography (TEG) (r 0.87-0.99, P>0.01 for all cases). OTEG angle was unaltered by anticoagulation whereas TEG angle presented a dose-dependent diminution probably linked to clot rupture. In both OTEG and TEG, MA was unaffected by heparin, argatroban or rivaroxaban. We conclude that OTEG can accurately monitor anticoagulation status following treatment, potentially providing a powerful tool for routine monitoring of patients in the doctor's office or in the home setting.

  19. Anticoagulation in the Elderly

    PubMed Central

    Robert-Ebadi, Helia; Righini, Marc

    2010-01-01

    Management of anticoagulation in elderly patients represents a particularly challenging issue. Indeed, this patient population is at high thromboembolic risk, but also at high hemorrhagic risk. Assessment of the benefit-risk balance of anticoagulation is the key point when decisions are made about introducing and/or continuing such treatments in the individual elderly patient. In order to maximise the safety of anticoagulation in the elderly, some specific considerations need to be taken into account, including renal insufficiency, modified pharmacodynamics of anticoagulants, especially vitamin K antagonists, and the presence of multiple comorbidities and concomitant medications. New anticoagulants could greatly simplify and possibly increase the safety of anticoagulation in the elderly in the near future.

  20. Dietary Vitamin K intake and anticoagulation control during the initiation phase of warfarin therapy: A prospective cohort study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of varying levels of dietary vitamin K intake on therapeutic International Normalized Ratio (INR) values among patients starting warfarin therapy has not been well studied. We performed a prospective cohort study among 282 patients to explore the independent associations between usual in...

  1. New Oral Anticoagulants in the Treatment of Pulmonary Embolism: Efficacy, Bleeding Risk, and Monitoring

    PubMed Central

    Rudd, Kelly M.; Phillips, Elizabeth (Lisa) M.

    2013-01-01

    Anticoagulation therapy is mandatory in patients with pulmonary embolism to prevent significant morbidity and mortality. The mainstay of therapy has been vitamin-K antagonist therapy bridged with parenteral anticoagulants. The recent approval of new oral anticoagulants (NOACs: apixaban, dabigatran, and rivaroxaban) has generated significant interest in their role in managing venous thromboembolism, especially pulmonary embolism due to their improved pharmacokinetic and pharmacodynamic profiles, predictable anticoagulant response, and lack of required efficacy monitoring. This paper addresses the available literature, on-going clinical trials, highlights critical points, and discusses potential advantages and disadvantages of the new oral anticoagulants in patients with pulmonary embolism. PMID:23691304

  2. Fatal pulmonary hemorrhage after taking anticoagulation medication

    PubMed Central

    Hammar, Samuel P.

    2015-01-01

    We describe a 64-year-old man with extensive diffuse acute lung hemorrhage, presumably as a result of anticoagulation therapy. We evaluated reports in the literature concerning acute exacerbation (acute lung injury of unknown cause) in UIP and other forms of fibrotic interstitial pneumonias. We also evaluated autopsy tissue in this case in order to determine the cause of death in this 64-year-old man, who was initially thought to have an asbestos-related disease. Based on the autopsy findings, this man died as a result of anticoagulation therapy; specifically, the use of Xarelto® (rivaroxaban). PMID:26236607

  3. [Extended options of anticoagulant treatment in thromboembolism].

    PubMed

    Karetová, Debora; Bultas, Jan

    2014-11-01

    Thromboembolic disease (TD) is a relatively common disease with acute risk of death and potential long-term consequences in term of postthrombotic syndrome or chronic pulmonary hypertension. Anticoagulant therapy is the basic therapeutic procedure; thrombolytic therapy and the introduction cava filter are appropriately indicated for individual cases. In past few years, new direct oral anticoagulant drugs (NOAC) have occurred - Xa factor or thrombin inhibitors which have demonstrated the same efficacy and even higher safety in comparison to conventional treatment. In mid 2014, 3 drugs of this group are registered in Czech Republic - rivaroxaban (Xarelto®), dabigatran (Pradaxa®) and apixaban (Eliquis®). These drugs have comparable efficacy and safety but they differ in schedule of dose administration. Rivaroxaban and apixaban can be administered immediately after diagnosis of venous thrombosis or hemodynamically stable pulmonary embolism. LMWH application has to precede few days the administration of dabigatran. Limitation of new drugs is their price. Unavailability of antidotes is temporary because current researches continue to find one for dabigatran and another for both of xabans. Duration of anticoagulant treatment after acute phase depends on the presence of thrombosis risk factors and the individual bleeding risk. Minimal duration of anticoagulant therapy is 3 months, commonly 6-12 months and in high risk patients it is "long term" treatment. Good results of new anticoagulant drugs in trials in term of thromboembolism recurrence prevention may change established habits in TD patients with long term treatment. PMID:25600045

  4. Newer Oral Anticoagulants: Stroke Prevention and Pitfalls

    PubMed Central

    Patel, Anand; Goddeau Jr, Richard P.; Henninger, Nils

    2016-01-01

    Warfarin is very effective in preventing stroke in patients with atrial fibrillation. However, its use is limited due to fear of hemorrhagic complications, unpredictable anticoagulant effects related to multiple drug interactions and dietary restrictions, a narrow therapeutic window, frequent difficulty maintaining the anticoagulant effect within a narrow therapeutic window, and the need for inconvenient monitoring. Several newer oral anticoagulants have been approved for primary and secondary prevention of stroke in patients with non-valvular atrial fibrillation. These agents have several advantages relative to warfarin therapy. As a group, these direct oral anticoagulants (DOAC), which include the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), are more effective than dose adjusted warfarin for prevention of all-cause stroke (including both ischemic and hemorrhagic stroke), and have an overall more favorable safety profile. Nevertheless, an increased risk of gastrointestinal bleeding (with the exception of apixaban), increased risk for thrombotic complication with sudden discontinuation, and inability to accurately assess and reverse anticoagulant effect require consideration prior to therapy initiation, and pose a challenge for decision making in acute stroke therapy. PMID:27347226

  5. Novel oral anticoagulants for atrial fibrillation

    PubMed Central

    How, Choon How

    2015-01-01

    Anticoagulation therapy is effective in preventing primary and secondary thromboembolic events due to atrial fibrillation. Warfarin, which was approved by the United States in 1954, was the only long-term oral anticoagulation therapy till the approval of dabigatran in 2010, and of rivaroxaban and other direct factor Xa inhibitors from 2011, forming a group known as novel oral anticoagulants (NOAC). NOAC have fewer food and drug interactions compared to warfarin; hence, the patient will require fewer clinic visits. However, the short half-life of NOAC means that twice-a-day dosing is needed and there is higher risk of a prothrombotic state when doses are missed. Other disadvantages are the lack of long-term data on NOAC, their high cost and the current lack of locally available antidotes. PMID:26702159

  6. [THE IMPORTANCE OF ANTICOAGULANT THERAPY IN PATIENTS WITH ARTIAL FIBRILLATION IN STROKE PREVENTION--SUMMARY OF INTERNATIONAL DATA AND NOVEL THERAPEUTIC MODALITIES].

    PubMed

    Mirolovics, Ágnes; Papp, Csaba; Zsuga, Judit; Bereczki, Dániel

    2016-03-30

    The most common cardiogenic cause of ischaemic stroke is atrial fibrillation which increases the probability of stroke five-fold and doubles case fatality. Based on international data the incidence of atrial fibrillation is approx. 2% however this rapidly increases with age. The necessity of using oral anticoagulants in the prevention of non-valvular atrial fibrillation related stroke is decided based on estimated stroke risk. The CHADS2 and the more predictive CHA2DS2-VASc scales are used for this purpose while the bleeding risk of patients treated with anticoagulant may be estimated by the HAS-BLED scoring scale. For decades oral anticoagulation meant using vitamin-K antagonists. Based on international data we can see that rate of anticoagulation is unacceptably low, furthermore most of the anticoagulated patients aren't within the therapeutic range of INR (INR: 2-3). A lot of disadvantages of vitamin-K antagonists are known (e.g. food-drug interaction, need for regular coagulation monitoring, increased risk of bleeding), therefore compounds with new therapeutic target have been developed. The novel oral anticoagulants (NOAC) can be divided in two major subgroups: direct thrombin inhibitors (dabigatran etexilate) and Xa-factor inhibitors (rivaroxaban, apixaban, edoxaban). These products are administered in fix doses, they less frequently interact with other medications or food, and regular coagulation monitoring is not needed when using these drugs. Moreover several studies have shown that they are at least as effective in the prevention of ischaemic stroke than the vitamin-K antagonists, with no more haemorrhagic complications. PMID:27188000

  7. Incidence of ischemic stroke and systemic embolism in patients with hypertrophic cardiomyopathy, nonvalvular atrial fibrillation, CHA2DS2-VASc score of ≤1 and without anticoagulant therapy.

    PubMed

    Yang, Yin-Jian; Yuan, Jin-Qing; Fan, Chao-Mei; Pu, Jie-Lin; Fang, Pi-Hua; Ma, Jian; Guo, Xi-Ying; Li, Yi-Shi

    2016-07-01

    Data on the risk of ischemic stroke and systemic embolism (iSSE) events in patients with nonvalvular atrial fibrillation (NVAF), a CHA2DS2-VASc score of ≤1, hypertrophic cardiomyopathy (HCM), and without anticoagulant therapy are still lacking. The aim of this study was to investigate the incidence of iSSE events in these patients. We consecutively screened medical records of patients with HCM and NVAF referred to Fuwai Hospital between January 1994 and March 2014. The primary end point was iSSE events, defined as a composite of ischemic stroke and systemic embolism. Follow-up was carried out to ascertain end point status. Medical records of 522 patients with NVAF and HCM were screened. A total of 108 patients (20.7 %) with a CHA2DS2-VASc score of ≤1 and without anticoagulant therapy were enrolled and constituted our study population. After a median follow-up of 2.4 years (range 0.6-14.1 years; 376.2 patient-years), ischemic stroke occurred in 2 patients, resulting in death of 1 patient in the first year and paralysis of the other patient in the fourth year. No other iSSE events occurred. The incidence of iSSE was 0.9 % [95 % confidence interval (CI) 0.0-5.0 %] in the first year, and 0.5 % per 100 patient-years (95 % CI 0.1-1.9 %). The risk of iSSE events seems low in patients with NVAF, a CHA2DS2-VASc score of ≤1, HCM, and without anticoagulant therapy. Multicenter studies with sizeable study populations are needed to validate the risk of iSSE events in these patients. PMID:26231425

  8. To anticoagulate or not to anticoagulate patients with cardiomyopathy.

    PubMed

    Graham, S P

    2001-11-01

    The current published literature does not indicate whether the long-term effect of anticoagulant or antiplatelet therapy contributes to mortality reduction in patients with LV dysfunction. Evaluating patients for personal risk for emboli or for ischemic coronary artery events may influence the choice of therapies. As more is learned about the mechanisms of drug effects in different populations, physicians may be better able to direct appropriate therapies. Until that time, one must weigh the risks and benefits of each drug alone and in combination. In NYHA class IV patients, the risk for thrombosis owing to spontaneous clotting increases as does the adverse potential of warfarin and the adverse effects of inhibiting prostaglandin mediated vasodilation by aspirin. In NYHA class I and II patients, the quality of life and convenience of multidrug therapy is weighed against the devastating effect of a major stroke. In less symptomatic patients, the long-term risk for acute coronary events may be higher than previously identified. This would suggest that all patients with depressed LV function should be on some type of antiplatelet or anticoagulant therapy. The current WATCH study will provide much needed information about the outcome differences between these agents. Conclusions based on available data include the following: Heart failure is increasing in incidence and prevalence. Atherosclerotic disease is an important causative factor for the development of heart failure or may be a comorbid condition in these patients. There is a measurable rate of stroke in patients with heart failure, although the cause of death in large studies is more often owing to sudden death or progressive heart failure. Sudden death may be from new ischemic events, asystole, or from ventricular tachyarrhythmias. In patients with heart failure, not all strokes are cardioembolic in origin. The benefits and risks of warfarin may be increased as the EF worsens or heart failure functional class

  9. Anticoagulant conversion in the elderly: pitfalls.

    PubMed

    Al-Nasser, Bassam

    2016-05-01

    The prevalence of medical conditions representing a risk for thromboembolic complications and requiring antithrombotic therapy increases gradually with age. Two cases of fatal noncritical organ bleeding complication that occurred during the conversion period from initial fondaparinux to vitamin K antagonist are presented. An 81-year-old obese female patient (body mass index 43 kg/m(2)) with previous postoperative thrombosis underwent uneventful total knee replacement under spinal anesthesia. She presented with popliteal hematoma during conversion to oral anticoagulant. A 92-year-old female patient (body mass index 33 kg/m(2)) with left lower limb thrombosis was referred to our orthopedics department from her senior citizens' home for right lower limb hematoma and ischemia that occurred during conversion to oral anticoagulant. Thromboembolic and bleeding events in the elderly are real public health problems. Specific guidelines dedicated to this particular population are needed, which will improve the management of anticoagulation and decrease risk of complications. PMID:26547115

  10. New anticoagulants for the treatment of venous thromboembolism

    PubMed Central

    Fernandes, Caio Julio Cesar dos Santos; Júnior, José Leonidas Alves; Gavilanes, Francisca; Prada, Luis Felipe; Morinaga, Luciana Kato; Souza, Rogerio

    2016-01-01

    Worldwide, venous thromboembolism (VTE) is among the leading causes of death from cardiovascular disease, surpassed only by acute myocardial infarction and stroke. The spectrum of VTE presentations ranges, by degree of severity, from deep vein thrombosis to acute pulmonary thromboembolism. Treatment is based on full anticoagulation of the patients. For many decades, it has been known that anticoagulation directly affects the mortality associated with VTE. Until the beginning of this century, anticoagulant therapy was based on the use of unfractionated or low-molecular-weight heparin and vitamin K antagonists, warfarin in particular. Over the past decades, new classes of anticoagulants have been developed, such as factor Xa inhibitors and direct thrombin inhibitors, which significantly changed the therapeutic arsenal against VTE, due to their efficacy and safety when compared with the conventional treatment. The focus of this review was on evaluating the role of these new anticoagulants in this clinical context. PMID:27167437

  11. [New anticoagulants in the treatment of venous thromboembolism].

    PubMed

    Bura-Rivière, Alessandra

    2013-09-01

    Anticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). The treatment needs rapid initial anticoagulaton to minimize the risk of thrombus extension and fata pulmonary embolism, followed by an extended anticoagulation, aimed at preventing recurrent VTE. Till very recently, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists, such as warfarin. Emerging direct oral anticoagulants have the potential to streamline VTE treatment. These agents include oral anticoagulants that target thrombin or factor Xa. This article reviews the characteristics of these agents, describes the results of clinical trials in venous thromboembolic disease and outlines their strengths and weakness. PMID:24167902

  12. Pharmacogenetics of oral anticoagulants.

    PubMed

    Daly, Ann K; King, Barry P

    2003-05-01

    There is wide interindividual variation in oral anticoagulant dose requirement, which is partly genetically determined. Several cytochrome P450s contribute to oxidative metabolism of oral anticoagulants. The most important of these is CYP2C9, which hydroxylates the S-enantiomers of warfarin, acenocoumarol and phenprocoumon with high catalytic activity. In at least eight separate clinical studies, possession of the CYP2C9*2 or CYP2C9*3 variant alleles, which result in decreased enzyme activity, has been associated with a significant decrease in a mean warfarin dose requirement. Several studies also suggest that possession of a CYP2C9 variant allele is associated with an increased risk of adverse events, such as bleeding. Possession of the CYP2C9*3 variant also appears to be associated with a low acenocoumarol dose requirement. Other genetic factors, such as polymorphisms in the cytochromes P450 that metabolize the R-enantiomers of warfarin and acenocoumarol, may also be relevant to anticoagulant dose. The molecular basis of anticoagulant resistance where a higher than normal dose of anticoagulant is required remains unclear, but could be due to unusually high CYP2C9 activity (pharmacokinetic resistance) or to an abnormality in the target enzyme vitamin K epoxide reductase (pharmacodynamic resistance). PMID:12724615

  13. Lupus anticoagulants and antiphospholipid antibodies

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000547.htm Lupus anticoagulants and antiphospholipid antibodies To use the sharing features on this page, please enable JavaScript. Lupus anticoagulants are antibodies against substances in the lining ...

  14. The new oral anticoagulants.

    PubMed

    Garcia, David; Libby, Edward; Crowther, Mark A

    2010-01-01

    Although their first application in clinical practice occurred in the 1940s, vitamin K antagonists remain the only form of oral anticoagulant medication approved for long-term use. Although the available vitamin K antagonists are highly effective for the prevention and/or treatment of most thrombotic disease, the significant interpatient and intrapatient variability in dose-response, the narrow therapeutic index, and the numerous drug and dietary interactions associated with these agents have led clinicians, patients, and investigators to search for alternative agents. Three new orally administered anticoagulants (apixaban, dabigatran, and rivaroxaban) are in the late stages of development and several others are just entering (or moving through) earlier phases of investigation. These novel anticoagulant medications are being studied for the prevention and treatment of venous thromboembolism, the treatment of acute coronary syndromes and the prevention of stroke in patients with atrial fibrillation. This review summarizes published clinical trial data pertinent to apixaban, dabigatran, and rivaroxaban. PMID:19880491

  15. "Timing" of arrival and in-hospital mortality in a cohort of patients under anticoagulant therapy presenting to the emergency departments with cerebral hemorrhage: A multicenter chronobiological study in Italy.

    PubMed

    Fabbian, Fabio; Manfredini, Roberto; De Giorgi, Alfredo; Gallerani, Massimo; Cavazza, Mario; Grifoni, Stefano; Fabbri, Andrea; Cervellin, Gianfranco; Ferrari, Anna Maria; Imberti, Davide

    2016-01-01

    Therapy with oral anticoagulants (OACs) is a risk factor for cerebral hemorrhage (CH). Although different studies have been undertaken to investigate the timing of the onset of major cardiovascular events, no data exist on temporal patterns of the onset of CH in subjects treated with OACs. The aim of this study is to evaluate the timing of CH in patients treated with OACs. All patients who developed CH under OACs therapy and admitted to 28 Italian Emergency Departments (EDs) between September 2011 and July 2013 were enrolled. Age, sex, time and location of the hemorrhagic lesion, type of the bleeding events (idiopathic or post-traumatic), anticoagulant therapy (warfarin or new oral anticoagulants - NOAs) and time of ED admission (i.e., hour, day, month and season) were recorded. Five hundred and seventeen patients (63.2% male aged 80 ± 7.9 yrs) with CH were involved. Warfarin was taken by 494 patients (95.6%), and NOAs by 23 (4.4%). In-hospital mortality (IHM) was recorded in 208 cases (40.2%). Cosinor analysis showed a peak of CH arrival between 12:00 and 14:00 h both in the whole population (PR 73.9%, p = 0.002) and the male subgroup (PR 65.2%, p = 0.009), whereas females showed an anticipated morning peak between 08:00 and 10:00 h (PR 65.7%, p = 0.008). A further analysis between idiopathic and post-traumatic CH confirmed the presence of a 24 h pattern with a peak between 12:00 and 14:00 h (PR 58.5%, p = 0.019) and between 08:00 and 10:00 h (PR80.1%, p < 0.001) for idiopathic events and post-traumatic hemorrhages, respectively. Moreover, a seasonal winter peak was identified for idiopathic forms (PR 74%, p = 0.035), and a summer peak for post-traumatic forms (PR 77%, p = 0.025). The present study suggests the presence of a temporal pattern of ED arrivals in CH patients treated with OACs. PMID:26852790

  16. New oral anticoagulants in atrial fibrillation.

    PubMed

    Turpie, Alexander G G

    2008-01-01

    Atrial fibrillation (AF) is a major risk factor for stroke. Currently, acetylsalicylic acid (a platelet inhibitor) and vitamin K antagonists (VKAs; oral anticoagulants), including warfarin, are the only approved antithrombotic therapies for stroke prevention in patients with AF. Although effective, VKAs have unpredictable pharmacological effects, requiring regular coagulation monitoring and dose adjustment to maintain effects within the therapeutic range. The clinical development pathway for novel anticoagulants often involves evaluation of efficacy and safety in a short-term indication, such as the prevention of venous thrombo-embolism (VTE), followed by longer-term VTE treatment studies, and finally chronic indications, including stroke prevention studies in patients with AF. The coagulation pathway provides many targets for novel anticoagulants, including Factor Xa (FXa) and Factor IIa (thrombin). Numerous oral, direct FXa inhibitors are in various stages of clinical development, including rivaroxaban, LY517717, YM150, DU-176b, apixaban, and betrixaban, and are anticipated to overcome the limitations of VKAs. Dabigatran is the only oral direct thrombin inhibitor in late-stage development. Studies of these agents for stroke prevention in patients with AF are planned or ongoing. If approved, they may represent the next generation of anticoagulants, by providing new therapeutic options for stroke prevention in patients with AF. PMID:18096568

  17. Antiplatelet and Anticoagulant Drugs in Interventional Radiology

    SciTech Connect

    Altenburg, Alexander; Haage, Patrick

    2012-02-15

    In treating peripheral arterial disease, a profound knowledge of antiplatelet and anticoagulative drug therapy is helpful to assure a positive clinical outcome and to anticipate and avoid complications. Side effects and drug interactions may have fatal consequences for the patient, so interventionalists should be aware of these risks and able to control them. Aspirin remains the first-line agent for antiplatelet monotherapy, with clopidogrel added where dual antiplatelet therapy is required. In case of suspected antiplatelet drug resistance, the dose of clopidogrel may be doubled; prasugrel or ticagrelor may be used alternatively. Glycoprotein IIb/IIIa inhibitors (abciximab or eptifibatide) may help in cases of hypercoagulability or acute embolic complications. Desmopressin, tranexamic acid, or platelet infusions may be used to decrease antiplatelet drug effects in case of bleeding. Intraprocedurally, anticoagulant therapy treatment with unfractionated heparin (UFH) still is the means of choice, although low molecular-weight heparins (LMWH) are suitable, particularly for postinterventional treatment. Adaption of LMWH dose is often required in renal insufficiency, which is frequently found in elderly patients. Protamine sulphate is an effective antagonist for UFH; however, this effect is less for LMWH. Newer antithrombotic drugs, such as direct thrombin inhibitors or factor X inhibitors, have limited importance in periprocedural treatment, with the exception of treating patients with heparin-induced thrombocytopenia (HIT). Nevertheless, knowing pharmacologic properties of the newer drugs facilitate correct bridging of patients treated with such drugs. This article provides a comprehensive overview of antiplatelet and anticoagulant drugs for use before, during, and after interventional radiological procedures.

  18. Newer anticoagulants in 2009.

    PubMed

    Samama, Meyer Michel; Gerotziafas, Grigoris T

    2010-01-01

    Several newer anticoagulants are under clinical development. Recently two of them, Dabigatran etexilate/Pradaxa. and Rivaroxaban/Xarelto obtained marketing authorization in Europe and Canada for the prevention of thromboembolic events following major orthopedic surgery such as total hip and knee replacement. The results of Phase III clinical studies in thromboprophylaxis in major orthopedic surgery are highlighted and discussed in detail. Ongoing Phase II and III clinical trials assess their efficacy in the secondary prevention and treatment of deep vein thrombosis and pulmonary embolism, and in the long-term prevention of stroke in patients with non-valvular atrial fibrillation and in combination with aspirin and clopidogrel in patients with acute coronary syndromes. Many other small antithrombotic molecules including a new generation of low molecular weight heparins, are currently in different stages of clinical development. In addition to being administered orally, the newer anticoagulant agents have a more balanced benefit/risk ratio and wider therapeutic window. They have a rapid onset of action, a predictable anticoagulant effect that does not require routine laboratory monitoring. They have minor food and drug interactions, including those with cytochrome P450 and P.gp. They are highly specific and targeted to a single coagulation factor, and could carry similar or less hemorrhagic risks compared to the older anticoagulant agents. Finally, they may be used in a broader variety of patients, especially the medically ill patients with advanced cancer, and the elderly without any dosage adjustment, regardless of the patient age, gender, body weight, or in patients with mild renal impairment. Their use in the general world will hopefully confirm the promising results of clinical trials. PMID:19838770

  19. Reimagining Anticoagulation Clinics in the Era of Direct Oral Anticoagulants.

    PubMed

    Barnes, Geoffrey D; Nallamothu, Brahmajee K; Sales, Anne E; Froehlich, James B

    2016-03-01

    Anticoagulation clinics were initially developed to provide safe and effective care for warfarin-treated patients with atrial fibrillation, venous thromboembolism, and mechanical valve replacement. Traditionally, these patients required ongoing laboratory monitoring and warfarin dose adjustment by expert providers. With the introduction of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban), many have questioned the need for anticoagulation clinic. However, we think that the growing number of oral anticoagulant choices creates an urgent need for expanding the traditional role of the anticoagulation clinic. We outline 3 key purposes that a reimagined anticoagulation clinic would serve: (1) to assist patients and clinicians with selecting the most appropriate drug and dose from a growing list of anticoagulant options (including warfarin), (2) to help patients minimize the risk of serious bleeding complications with careful long-term monitoring and peri-procedural management, and (3) to encourage ongoing adherence to these life-saving medications. We also describe how repurposing anticoagulation clinics as broader medication safety clinics would promote safe and effective care across a range of cardiovascular conditions for high-risk medications (eg, spironolactone, amiodarone). Finally, we highlight a few existing health systems that are overcoming key challenges to implementing a reimagined anticoagulation or medication safety clinic structure. PMID:26933047

  20. Citrate anticoagulation in the ICU: the Leeds experience.

    PubMed

    Trumper, Charlotte

    2016-09-01

    Continuous renal replacement therapy (CRRT) is widely used in the management of critically ill patients with acute kidney injury. It requires effective anticoagulation of the extracorporeal blood circuit. Although heparin is the most commonly prescribed anticoagulant, there are issues associated with heparin, and there has been increasing interest in regional citrate anticoagulation as an alternative. In 2013, The Leeds Teaching Hospitals NHS Trust switched from heparin to citrate anticoagulant for CRRT in intensive care units (ICUs) across the Trust. This article examines the reasons for the switch, the implementation of citrate and the impact of this quality-improvement project in terms of patient outcome data and feedback from the ICU nursing team. PMID:27615524

  1. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

    PubMed

    Garcia, David A; Baglin, Trevor P; Weitz, Jeffrey I; Samama, Meyer Michel

    2012-02-01

    This article describes the pharmacology of approved parenteral anticoagulants. These include the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid, as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin, factor Xa, and other clotting enzymes. Heparin also binds to cells and plasma proteins other than antithrombin causing unpredictable pharmacokinetic and pharmacodynamic properties and triggering nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and plasma proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and are associated with a lower risk of nonhemorrhagic side effects. LMWHs can be administered once daily or bid by subcutaneous injection, without coagulation monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin. Therefore, fondaparinux-associated HIT or osteoporosis is unlikely to occur. Fondaparinux exhibits complete bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without coagulation monitoring. Three additional parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in patients with HIT. PMID:22315264

  2. D-dimer and factor VIIa in atrial fibrillation - prognostic values for cardiovascular events and effects of anticoagulation therapy. A RE-LY substudy.

    PubMed

    Siegbahn, Agneta; Oldgren, Jonas; Andersson, Ulrika; Ezekowitz, Michael D; Reilly, Paul A; Connolly, Stuart J; Yusuf, Salim; Wallentin, Lars; Eikelboom, John W

    2016-05-01

    Coagulation markers may improve monitoring the risk of stroke and bleeding in patients with atrial fibrillation (AF) during anticoagulant treatment. We examined baseline levels of D-dimer and their association with stroke, cardiovascular death and major bleeding in 6,202 AF patients randomised to dabigatran or warfarin in the RE-LY trial. The effects of treatment on serial levels of D-dimer and coagulation factor (F) VIIa in 2,567 patients were also analysed. Baseline D-dimer levels were related to the rate of stroke/systemic embolism (SEE) with 0.64 % in the lowest quartile (Q1, as reference) (D-dimer < 298 µg/l), 1.38 % Q2 (D-dimer 298-473 µg/l), 1.71 % Q3 (D-dimer 474-822 µg/l) and 2.00 % in Q4 (D-dimer > 822 µg/l) (p=0.0007). Similar associations were shown for cardiovascular death and major bleeding. Addition of baseline D-dimer to established clinical risk factors improved prediction of stroke/SEE, cardiovascular death and major bleeding (C-index increased from 0.66 to 0.68, 0.71 to 0.73 and 0.66 to 0.67, respectively). Dabigatran provided a greater reduction of D-dimer levels than warfarin regardless of baseline anticoagulant treatment. On-treatment levels of FVIIa were markedly reduced by warfarin (median 12.1-13.8 mU/ml) but significantly higher with dabigatran (median 39.4-49.0 mU/ml) at all-time points. Dabigatran is associated with greater reduction in D-dimer without the pronounced reduction of FVIIa seen with warfarin. These different effects on the coagulation system might explain the better efficacy and less intracranial bleeding observed with dabigatran compared with warfarin. PMID:26818781

  3. Simplified Citrate Anticoagulation for CRRT Without Calcium Replacement.

    PubMed

    Broman, Marcus; Klarin, Bengt; Sandin, Karin; Carlsson, Ola; Wieslander, Anders; Sternby, Jan; Godaly, Gabriela

    2015-01-01

    Since 2012, citrate anticoagulation is the recommended anticoagulation strategy for continuous renal replacement therapy (CRRT). The main drawback using citrate as anticoagulant compared with heparin is the need for calcium replacement and the rigorous control of calcium levels. This study investigated the possibility to achieve anticoagulation while eliminating the need for calcium replacement. This was successfully achieved by including citrate and calcium in all CRRT solutions. Thereby the total calcium concentration was kept constant throughout the extracorporeal circuit, whereas the ionized calcium was kept at low levels enough to avoid clotting. Being a completely new concept, only five patients with acute renal failure were included in a short, prospective, intensely supervised nonrandomized pilot study. Systemic electrolyte levels and acid-base parameters were stable and remained within physiologic levels. Ionized calcium levels declined slightly initially but stabilized at 1.1 mmol/L. Plasma citrate concentrations stabilized at approximately 0.6 mmol/L. All postfilter ionized calcium levels were <0.5 mmol/L, that is, an anticoagulation effect was reached. All filter pressures were normal indicating no clotting problems, and no visible clotting was observed. No calcium replacement was needed. This pilot study suggests that it is possible to perform regional citrate anticoagulation without the need for separate calcium infusion during CRRT. PMID:25851312

  4. Underuse of anticoagulation in patients with atrial fibrillation.

    PubMed

    Vallakati, Ajay; Lewis, William R

    2016-01-01

    Atrial fibrillation (AF) is a major risk factor for ischemic stroke. Guidelines recommend anticoagulation for patients with intermediate and high stroke risk (CHA2DS2-VASc score ≥ 2). Underuse of anticoagulants among eligible patients remains a persistent problem. Evidence demonstrates that the psychology of the fear of causing harm (omission bias) results in physicians' hesitancy to initiate anticoagulation and an inaccurate estimation of stroke risk. The American Heart Association (AHA) initiated the Get With The Guidelines-AFIB (GWTG-AFIB) module in June 2013 to enhance guideline adherence for treatment and management of AF. Better quality of care for AF patients can be provided by increasing adherence to anticoagulation guidelines and improving patient compliance with anticoagulation therapy through education and established protocols. Nonvitamin K antagonist oral anticoagulants may facilitate better patient adherence due to ease of administration and reduced monitoring burden. In this review, we discuss the reasons for underuse, omission bias contributing to underuse, and different strategies to address this issue. PMID:26666288

  5. New anticoagulants for the prevention of venous thromboembolism

    PubMed Central

    Becattini, Cecilia; Lignani, Alessandra; Agnelli, Giancarlo

    2010-01-01

    Anticoagulant drugs have an essential role in the prevention and treatment of thromboembolic diseases. Currently available anticoagulants substantially reduce the incidence of thromboembolic events in a number of clinical conditions. However, these agents have limitations that strengthen the case for the development of new anticoagulants. An ideal anticoagulant should be at least as effective as those currently in use, as well as safe, simple to use, and widely applicable. The majority of new anticoagulants currently under investigation are small molecules with a selective and direct anti-Xa or antithrombin action, allowing oral administration in fixed doses. These new agents are in different phases of clinical development. The anti-Xa agent rivaroxaban and the antithrombin agent dabigatran are already available for the prophylaxis of venous thromboembolism in some countries. Apixaban is in an advanced phase of clinical development and several anti-Xa agents are currently approaching phase III clinical trials. Promising results in terms of efficacy and safety profiles have been obtained with these agents in different clinical conditions. Differences in pharmacokinetics and pharmacodynamics could offer the potential for individualized anticoagulant therapies in the near future. PMID:20531960

  6. Anticoagulants versus cancer.

    PubMed

    Tieken, Chris; Versteeg, Henri H

    2016-04-01

    Venous thromboembolism (VTE) and cancer are strongly associated, and present a major challenge in cancer patient treatment. Cancer patients have a higher risk of developing VTE, although the risk differs widely between tumour types. VTE prophylaxis is routinely given to cancer patients, in the form of vitamin K antagonists (VKA) or low molecular weight heparin (LMWH). Several studies have reported that cancer patients receiving anticoagulants show prolonged survival and this effect was more pronounced in patients with a good prognosis, although the mechanism is poorly understood. Tissue Factor (TF) is the initiator of extrinsic coagulation, but its non-haemostatic signalling via protease-activated receptors (PARs) is a potent driver of tumour angiogenesis. Furthermore, coagulation activation is strongly implicated in tumour cell migration and metastasis. This review discusses the effects of anticoagulants on cancer progression in patients, tumour cell behaviour, angiogenesis, and metastasis in in vitro and in vivo models. Inhibition of TF signalling shows great promise in curbing angiogenesis and in vivo tumour growth, but whether this translates to patients is not yet known. Furthermore, non-haemostatic properties of coagulation factors in cancer progression are discussed, which provide exciting opportunities on limiting oncologic processes without affecting blood coagulation. PMID:27067969

  7. Factors affecting the quality of anticoagulation with warfarin: experience of one cardiac centre

    PubMed Central

    Ciurus, Tomasz; Cichocka-Radwan, Anna

    2015-01-01

    Introduction The risk of complications in anticoagulation therapy can be reduced by maximising the percentage of time spent by the patient in the optimal therapeutic range (TTR). However, little is known about the predictors of anticoagulation control. The aim of this paper was to assess the quality of anticoagulant therapy in patients on warfarin and to identify the factors affecting its deterioration. Material and methods We studied 149 patients who required anticoagulant therapy with warfarin due to non-valvular atrial fibrillation and/or venous thromboembolism. Each patient underwent proper training regarding the implemented treatment and remained under constant medical care. Results The mean age of the patients was 68.8 ± 12.6 years, and 59% were male. A total of 2460 international normalised ratio (INR) measurements were collected during the 18-month period. The mean TTR in the studied cohort was 76 ± 21%, and the median was 80%. The level at which high-quality anticoagulation was recorded for this study was based on TTR values above 80%. Seventy-five patients with TTR ≥ 80% were included in the stable anticoagulation group (TTR ≥ 80%); the remaining 74 patients constituted the unstable anticoagulation group (TTR < 80%). According to multivariate stepwise regression analysis, the independent variables increasing the risk of deterioration of anticoagulation quality were: arterial hypertension (OR 2.74 [CI 95%: 1.06-7.10]; p = 0.038), amiodarone therapy (OR 4.22 [CI 95%: 1.30-13.70]; p = 0.017), and obesity (OR 1.11 [CI 95%: 1.02-1.21]; p = 0.013). Conclusions The presence of obesity, hypertension, or amiodarone therapy decreases the quality of anticoagulation with warfarin. High quality of anticoagulation can be achieved through proper monitoring and education of patients. PMID:26855650

  8. Comparing new anticoagulants.

    PubMed

    Wooten, James M

    2012-12-01

    For years, the pharmaceutical industry has been trying to find a safe and effective drug to replace warfarin. Although warfarin is an effective anticoagulant, its pharmacology, adverse effects, and risk profiles dictate that patients taking this medication must be monitored judiciously. The US Food and Drug Administration has approved two drugs for commercial use, dabigatran and rivaroxaban, that will compete directly with warfarin for use in specific indications. Because of direct marketing to patients, physicians are being asked to comment on these new medications. This brief review illustrates the data available for the two new drugs when compared to warfarin for the specified indications. For some patients, these drugs may be highly beneficial and offer an excellent alternative to warfarin. For others, warfarin may still be the preferred drug. PMID:23211502

  9. Avulsion of the auricle in an anticoagulated patient: is leeching contraindicated? A review and a case.

    PubMed

    Mommsen, Jens; Rodríguez-Fernández, Javier; Mateos-Micas, Mario; Vázquez-Bouso, Olga; Gumbao-Grau, Victor; Forteza-Gonzalez, Gabriel

    2011-06-01

    Amputation of the auricle is a periodic occurrence leading to disfigurement if not treated properly. Venous stasis is a common complication in reattachments and requires decongestant and anticoagulant treatment. Today, leech therapy is the treatment of choice. Common problems are that it is not available everywhere and that it is usually contraindicated in anticoagulated patients. The peculiarities of leech therapy and the various aspects of surgical management are reviewed. A case of a partial amputation of the auricle in a patient under concomitant anticoagulation therapy with warfarin is presented. The amputated part was reattached in another hospital without microvascular anastomosis. The patient presented to our department with early signs of venous congestion. Leech therapy was started 35 hours after trauma, and the patient continued his anticoagulation therapy. With this treatment, 90% of the amputated part was rescued. The anticoagulation therapy of the patient may have played an important role in the first hours after reattachment, preventing capillary thrombosis and in consequence facilitating the minimal oxygenation necessary. The claim that anticoagulation therapy is a contraindication to leeching should be questioned in cases of reattachments in well-controllable locations without arterial anastomosis. PMID:22655116

  10. Avulsion of the Auricle in an Anticoagulated Patient: Is Leeching Contraindicated? A Review and a Case

    PubMed Central

    Mommsen, Jens; Rodríguez-Fernández, Javier; Mateos-Micas, Mario; Vázquez-Bouso, Olga; Gumbao-Grau, Victor; Forteza-Gonzalez, Gabriel

    2011-01-01

    Amputation of the auricle is a periodic occurrence leading to disfigurement if not treated properly. Venous stasis is a common complication in reattachments and requires decongestant and anticoagulant treatment. Today, leech therapy is the treatment of choice. Common problems are that it is not available everywhere and that it is usually contraindicated in anticoagulated patients. The peculiarities of leech therapy and the various aspects of surgical management are reviewed. A case of a partial amputation of the auricle in a patient under concomitant anticoagulation therapy with warfarin is presented. The amputated part was reattached in another hospital without microvascular anastomosis. The patient presented to our department with early signs of venous congestion. Leech therapy was started 35 hours after trauma, and the patient continued his anticoagulation therapy. With this treatment, 90% of the amputated part was rescued. The anticoagulation therapy of the patient may have played an important role in the first hours after reattachment, preventing capillary thrombosis and in consequence facilitating the minimal oxygenation necessary. The claim that anticoagulation therapy is a contraindication to leeching should be questioned in cases of reattachments in well-controllable locations without arterial anastomosis. PMID:22655116

  11. Antithrombotic therapy use in patients with atrial fibrillation before the era of non-vitamin K antagonist oral anticoagulants: the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) Phase I cohort

    PubMed Central

    Huisman, Menno V.; Ma, Chang Sheng; Diener, Hans-Christoph; Dubner, Sergio J.; Halperin, Jonathan L.; Rothman, Kenneth J.; Teutsch, Christine; Schoof, Nils; Kleine, Eva; Bartels, Dorothee B.; Lip, Gregory Y.H.

    2016-01-01

    Aims The introduction of non-VKA oral anticoagulants (NOACs), which differ from the earlier vitamin K antagonist (VKA) treatments, has changed the approach to stroke prevention in atrial fibrillation (AF). GLORIA-AF is a prospective, global registry programme describing the selection of antithrombotic treatment in newly diagnosed AF patients at risk of stroke. It comprises three phases: Phase I, before the introduction of NOACs; Phase II, during the time of the introduction of dabigatran, the first NOAC; and Phase III, once NOACs have been established in clinical practice. Methods and results In Phase I, 1063 patients were eligible from the 1100 enrolled (54.3% male; median age 70 years); patients were from China (67.1%), Europe (EU; 27.4%), and the Middle East (ME; 5.6%). The majority of patients using VKAs had high stroke risk (CHA2DS2-VASc ≥ 2; 86.5%); 13.5% had moderate risk (CHA2DS2-VASc = 1). Vitamin K antagonist use was higher for persistent/permanent AF (47.7%) than that for paroxysmal (23.9%). Most patients in China were treated with antiplatelet agents (53.7%) vs. 27.1% in EU and 28.8% in ME. In China, 25.9% of patients had no antithrombotic therapy, vs. 8.6% in EU and 8.5% in ME. Conclusion Phase I of GLORIA-AF shows that VKAs were mostly used in patients with persistent/permanent (vs. paroxysmal) AF and in those with high stroke risk. Furthermore, there were meaningful geographical differences in the use of VKA therapy in the era before the availability of NOACs, including a much lower use of VKAs in China, where most patients either received antiplatelet agents or no antithrombotic treatment. PMID:27335063

  12. The use of anticoagulation in pediatric cardiac disease

    PubMed Central

    Boris, JR; Harris, MA

    2003-01-01

    Palliation and repair of increasingly complex congenital heart defects as well as the emergence of novel contexts has led to multiple scenarios in which a real or potential risk of thromboembolism may exist. While various anticoagulation methodologies have been well defined for adults, there are few studies relating directly to pediatric patients. This article reviews a number of specific pediatric disease states, the representative pediatric literature, and, where appropriate, the corresponding adult literature. In so doing, the art and science of pediatric cardiac anticoagulation is defined with the hope to engender further thought regarding future directions of study and therapy. PMID:22368628

  13. A pharmacologic overview of current and emerging anticoagulants.

    PubMed

    Nutescu, Edith A; Shapiro, Nancy L; Chevalier, Aimee; Amin, Alpesh N

    2005-04-01

    For over 50 years, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to traditional agents such as unfractionated heparin and oral vitamin K antagonists such as warfarin. These traditional agents are fraught with limitations that complicate their clinical use. A variety of novel anticoagulants with improved pharmacologic and clinical profiles have recently been introduced or are in development, offering benefits over traditional therapies. Specifically, progress has been made in the development of low-molecular-weight heparins, factor Xa inhibitors, and direct thrombin inhibitors. Because of their convenience and ease of use, some of these novel compounds are competing with the traditional anticoagulants and are needed additions to the antithrombotic arsenal. PMID:15853173

  14. Platelet aggregation in presence of anticoagulants dependent pseudothrombocytopenia.

    PubMed

    D'Angelo, G; Calvano, D; Mattaini, R; Cosini, I; Giardini, C

    1993-01-01

    We report a case of pseudothrombocytopenia anticoagulants dependence in a healthy woman. Platelet count was performed on the automated impedance haematological analyzer utilizing peripheral blood samples anticoagulated with ethylene diamine tetra-acetate, heparin and sodium citrate. We pointed out that the severe thrombocytopenia was principally time and ethylene diamine tetra-acetate dependent. As regard both the temperature (37 degrees C) and the other anticoagulants (heparin, sodium citrate), the phenomenon was variable. The phenomenon "in vitro" was confirmed by the normal aggregation, moreover we showed that the platelets of a normal subject aggregated with plasma and ethylene diamine tetra-acetate of pseudothrombocytopenic subject. We report this case because often, in a healthy subject, it is possible to make a mistake in diagnosis and to employ more sophisticated and expansive investigations. Moreover it is very important to point out the pseudothrombocytopenia in case of heparinic therapy because it is possible to have a dilated thrombocytopenia. PMID:8414132

  15. Management of hemorrhage with the target-specific oral anticoagulants.

    PubMed

    Pluym, Mark; Howell, Gregory

    2014-08-01

    The target-specific oral anticoagulants have recently been introduced as alternatives to warfarin for both prophylactic and therapeutic indications. Although their efficacy and side-effect profiles have been favorable, there is significant concern about management of hemorrhage with these agents as there is no direct reversal agent available. It is important for clinicians to be aware of these agents and the issues that surround them. Most of the management of hemorrhage is based on expert opinion and case reviews. Given the potentially catastrophic consequences of acute hemorrhage while patients are on anticoagulation, specific treatments are needed. Some methods that have been described include activated charcoal, hemodialysis, prohemostatic agents, and transfusions. Target-specific therapies have been shown to be effective in early studies in animal models; however, the effects in humans are still under investigation. More investigation is needed on the management of bleeding complications from target-specific oral anticoagulants. PMID:25255409

  16. Laparoscopic resection of a gastrointestinal stromal tumor of the lower rectum in a patient with coronary artery disease following long-term neoadjuvant imatinib treatment and anticoagulation therapy

    PubMed Central

    2014-01-01

    Surgery is the mainstay of treatment for gastrointestinal stromal tumors (GISTs). However, complete resection of rectal GISTs is sometimes difficult because of bulkiness and/or anatomical reasons. Neoadjuvant imatinib therapy has gained attention as an alternative treatment to increase the chance of en bloc resection of rectal GISTs, although it usually takes several months. In this case report, we first demonstrated that neoadjuvant imatinib therapy can be performed safely not only to downsize tumors, but also to allow adequate time for the effective treatment of major comorbid illnesses. A 74-year-old man was diagnosed with a 45 mm GIST of the lower rectum. He also had severe stenosis in the proximal segment of the left anterior descending coronary artery. Following the implantation of a drug-eluting stent, the patient received imatinib together with dual anti-platelet therapy for 12 months without obvious side effects. Follow-up image studies revealed tumor shrinkage as well as stent patency. En bloc resection of the GIST was performed laparoscopically, which preserved the anus. The patient is currently alive without any evidence of relapse for 12 months after surgery. PMID:25022862

  17. [The practice guideline 'Neuraxis blockade and anticoagulation'].

    PubMed

    De Lange, J J; Van Kleef, J W; Van Everdingen, J J E

    2004-07-31

    In a patient with a coagulation disorder, the administration of a local anaesthetic by means of a needle or via the insertion of a catheter into the epidural space or spinal cavity may lead to bleeding and haematoma formation, with a danger of pressure on the spinal cord or nerve roots. Employing the method of the Dutch Institute for Healthcare (CBO) for the development of practice guidelines, a working group of anaesthesiologists, a haematologist and a hospital chemist have drawn up recommendations for neuraxis blockade in combination with anticoagulant therapy. In patients with a clinically acquired tendency toward increased bleeding, the management is highly dependent on the cause of the bleeding tendency. If the patient uses acetylsalicylic acid or clopidogrel, the medication must be withdrawn at least 10 days before neuraxis blockade is started. Therapy with glycoprotein-IIb/IIIa-receptor antagonists is an absolute contra-indication for neuraxis blockade. In patients who are using coumarin derivatives, neuraxis blockade results in an increased risk of a neuraxial haematoma. The coumarin derivative should then be withdrawn and replaced by a different form of anticoagulation. The use of low-molecular-weight heparin at the usual prophylactic dosage is not a contra-indication for neuraxis blockade and the risk of a neuraxial haematoma following neuraxis blockade is also not increased significantly by the subcutaneous administration of unfractionated heparin. PMID:15366721

  18. Anticoagulation Considerations for Travel to High Altitude.

    PubMed

    DeLoughery, Thomas G

    2015-09-01

    DeLoughery, Thomas G. Anticoagulation considerations for travel to high altitude. High Alt Med Biol 16:181-185, 2015.-An increasing percentage of the population are on anticoagulation medicine for clinical reasons ranging from stroke prevention in atrial fibrillation to long term prevention of deep venous thrombosis. In recent years, several new direct oral anticoagulants have entered the market. The key questions that should be kept in mind when approaching a potential traveler on anticoagulation are: 1) why is the patient on anticoagulation? 2) do they need to stay on anticoagulation? 3) what are the choices for their anticoagulation? 4) will there be any drug interactions with medications needed for travel? and 5) how will they monitor their anticoagulation while traveling? Knowing the answers to these questions then can allow for proper counseling and planning for the anticoagulated traveler's trip. PMID:26186419

  19. Novel oral anticoagulants in acute coronary syndrome.

    PubMed

    Costopoulos, Charis; Niespialowska-Steuden, Maria; Kukreja, Neville; Gorog, Diana A

    2013-09-10

    Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide with a prevalence that has now reached pandemic levels as a consequence of the rapid modernization of the developing world. Its presentation as an acute coronary syndrome (ACS) is a frequent reason for hospital admission and of profound implications for personal, societal and global health. Despite improvements in the management of ACS with anti-platelet and anticoagulant therapy and revascularization techniques, many patients continue to suffer recurrent ischemic events. The need to reduce future cardiovascular events has led to the development of novel therapies to prevent coronary thrombosis, targeting thrombin-mediated pathways. These include direct Xa inhibitors (apixaban, rivaroxaban and darexaban), direct thrombin inhibitors (dabigatran) and PAR 1 antagonists (vorapaxar and atopaxar). This article critically reviews the comparative mechanisms of action, the risks and benefits, together with the clinical evidence base for the use of these novel oral agents in the management of ACS patients. PMID:22989603

  20. Reversing anticoagulant effects of novel oral anticoagulants: role of ciraparantag, andexanet alfa, and idarucizumab

    PubMed Central

    Hu, Tiffany Y; Vaidya, Vaibhav R; Asirvatham, Samuel J

    2016-01-01

    Novel oral anticoagulants (NOACs) are increasingly used in clinical practice, but lack of commercially available reversal agents is a major barrier for mainstream use of these therapies. Specific antidotes to NOACs are under development. Idarucizumab (aDabi-Fab, BI 655075) is a novel humanized mouse monoclonal antibody that binds dabigatran and reverses its anticoagulant effect. In a recent Phase III study (Reversal Effects of Idarucizumab on Active Dabigatran), a 5 g intravenous infusion of idarucizumab resulted in the normalization of dilute thrombin time in 98% and 93% of the two groups studied, with normalization of ecarin-clotting time in 89% and 88% patients. Two other antidotes, andexanet alfa (PRT064445) and ciraparantag (PER977) are also under development for reversal of NOACs. In this review, we discuss commonly encountered management issues with NOACs such as periprocedural management, laboratory monitoring of anticoagulation, and management of bleeding. We review currently available data regarding specific antidotes to NOACs with respect to pharmacology and clinical trials. PMID:26937198

  1. Utility of a dedicated pediatric cardiac anticoagulation program: the Boston Children's Hospital experience.

    PubMed

    Murray, Jenna M; Hellinger, Amy; Dionne, Roger; Brown, Loren; Galvin, Rosemary; Griggs, Suzanne; Mittler, Karen; Harney, Kathy; Manzi, Shannon; VanderPluym, Christina; Baker, Annette; O'Brien, Patricia; O'Connell, Cheryl; Almond, Christopher S

    2015-04-01

    Congenital heart disease is the leading cause of stroke in children. Warfarin therapy can be difficult to manage safely in this population because of its narrow therapeutic index, multiple drug and dietary interactions, small patient size, high-risk cardiac indications, and lack of data to support anticoagulation recommendations. We sought to describe our institution's effort to develop a dedicated cardiac anticoagulation service to address the special needs of this population and to review the literature. In 2009, in response to Joint Commission National Patient Safety Goals for Anticoagulation, Boston Children's Hospital created a dedicated pediatric Cardiac Anticoagulation Monitoring Program (CAMP). The primary purpose was to provide centralized management of outpatient anticoagulation to cardiac patients, to serve as a disease-specific resource to families and providers, and to devise strategies to evolve clinical care with rapidly emerging trends in anticoagulation care. Over 5 years the CAMP Service, staffed by a primary pediatric cardiology attending, a full-time nurse practitioner, and administrative assistant with dedicated support from pharmacy and nutrition, has enrolled over 240 patients ranging in age from 5 months to 55 years. The most common indications include a prosthetic valve (34 %), Fontan prophylaxis (20 %), atrial arrhythmias (11 %), cardiomyopathy (10 %), Kawasaki disease (7 %), and a ventricular assist device (2 %). A patient-centered multi-disciplinary cardiac anticoagulation clinic was created in 2012. Overall program international normalized ratio (INR) time in therapeutic range (TTR) is favorable at 67 % (81 % with a 0.2 margin) and has improved steadily over 5 years. Pediatric-specific guidelines for VKOR1 and CYP2C9 pharmacogenomics testing, procedural bridging with enoxaparin, novel anticoagulant use, and quality metrics have been developed. Program satisfaction is rated highly among families and providers. A dedicated pediatric

  2. Impact of Global Geographic Region on Time in Therapeutic Range on Warfarin Anticoagulant Therapy: Data From the ROCKET AF Clinical Trial

    PubMed Central

    Singer, Daniel E.; Hellkamp, Anne S.; Piccini, Jonathan P.; Mahaffey, Kenneth W.; Lokhnygina, Yuliya; Pan, Guohua; Halperin, Jonathan L.; Becker, Richard C.; Breithardt, Günter; Hankey, Graeme J.; Hacke, Werner; Nessel, Christopher C.; Patel, Manesh R.; Califf, Robert M.; Fox, Keith A. A.

    2013-01-01

    Background Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals. Conclusions Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:23525418

  3. Direct Oral Anticoagulants for the Management of Thromboembolic Disorders: The Importance of Adherence and Persistence in Achieving Beneficial Outcomes.

    PubMed

    Amin, Alpesh; Marrs, Joel C

    2016-10-01

    Anticoagulation therapy is central to the management of thromboembolic disorders, and the use of direct oral anticoagulants offers several advantages over standard therapy with parenteral heparins and vitamin K antagonists. In phase III clinical trials, the direct oral anticoagulants (given once or twice daily) all demonstrated favorable benefit-risk profiles compared with conventional standard therapy for the treatment and secondary prevention of venous thromboembolism and for stroke prevention in patients with nonvalvular atrial fibrillation. In clinical practice, many factors may influence overall clinical outcomes in patients receiving anticoagulant therapy, including adherence and persistence to the prescribed therapy, which becomes particularly important during long-term therapy. When choosing an anticoagulant for an individual patient, the pharmacological and clinical profile of the anticoagulant, its dosing regimen, and the patient's clinical characteristics (eg, renal function and comorbidities) and preferences should be considered. This review examines the rationale for and clinical evidence of the selected dosing regimens of the direct oral anticoagulants for the treatment of venous thromboembolism and stroke prevention in nonvalvular atrial fibrillation. The potential influence of dosing strategies (eg, once- or twice-daily dosing) and other factors on patient adherence and therapy persistence are also discussed. PMID:26316518

  4. Novel oral anticoagulants in cardiovascular disease.

    PubMed

    Gallego, Pilar; Roldán, Vanessa; Lip, Gregory Y H

    2014-01-01

    Nonvalvular atrial fibrillation (AF) confers an increased risk of thromboembolism, with a 5-fold higher risk of ischemic stroke. Oral anticoagulation (OAC) has shown to be highly effective in preventing stroke and mortality compared to placebo and is also used in patients without AF for both treatment and prophylaxis of venous thromboembolism. The OAC halts the coagulation by different mechanisms. Until recently, the only option was the vitamin K antagonists (VKAs), but their inherent limitations have promoted the development of novel oral anticoagulants (NOACs), which may offer efficacious and safer alternatives. Patients should be carefully selected to receive the most suitable treatment for each one. As the VKA efficacy and safety largely rely on the time the patient remains within the therapeutic range, this could be a useful selection criterion. Bleeding remains the main complication of all OACs. Although clinical trials of stroke prevention in AF have shown a significant reduction in hemorrhagic stroke and intracranial bleeding with the NOACs, as prescriptions are increasing, clinicians need to be prepared to accurate management of bleeding complications. Withholding the drug is usually enough for most cases of mild bleeding, but in patients with major, life-threatening bleeding, other measures, such as fluid replacement and blood transfusion, might be necessary while waiting for specific reversal agents that may reach the market soon. In case of acute bleeding, the accurate estimation of anticoagulant effect could also be needed, but the currently available coagulation tests only offer a qualitative measure. While awaiting long-term safety data, the choice between all these available therapies should be based on patient preferences, compliance, and ease of administration as well as on local factors affecting cost-effectiveness. But the increasing variety of therapeutic options when chronic OAC is needed can only improve the provided health care. PMID

  5. Unfavourable effects of medically indicated oral anticoagulants on survival in idiopathic pulmonary fibrosis.

    PubMed

    Kreuter, Michael; Wijsenbeek, Marlies S; Vasakova, Martina; Spagnolo, Paolo; Kolb, Martin; Costabel, Ulrich; Weycker, Derek; Kirchgaessler, Klaus-Uwe; Maher, Toby M

    2016-06-01

    Procoagulant and antifibrinolytic activity has been associated with idiopathic pulmonary fibrosis (IPF); however, investigation of anticoagulant therapy in IPF has suggested deleterious effects. This post hoc analysis evaluated the effect of medically indicated anticoagulation on mortality and other clinical outcomes in IPF.Patients randomised to placebo (n=624) from three controlled trials in IPF were analysed by oral anticoagulant use. End-points included all-cause and IPF-related mortality, disease progression, hospitalisation, and adverse events, over 1 year.At baseline, 32 (5.1%) patients randomised to placebo were prescribed anticoagulants for non-IPF indications, 29 (90.6%) of whom received warfarin. Unadjusted analyses demonstrated significantly higher all-cause and IPF-related mortality at 1 year in baseline anticoagulant users versus nonusers (15.6% versus 6.3%, p=0.039 and 15.6% versus 3.9%, p=0.002, respectively). In multivariate analyses, baseline use of anticoagulants was an independent predictor of IPF-related mortality (hazard ratio 4.7, p=0.034), but not other end-points. Rates of bleeding and cardiac events did not differ significantly between groups. In an exploratory analysis, anticoagulant use at any time during the study was an independent predictor of all end-points.This post hoc analysis suggests that anticoagulants used for non-IPF indications may have unfavourable effects in IPF patients. Future studies are needed to explore this relationship further. PMID:27103382

  6. Anticoagulation in atrial fibrillation. Is there a gap in care for ambulatory patients?

    PubMed Central

    Putnam, Wayne; Nicol, Kelly; Anderson, David; Brownell, Brenda; Chiasson, Meredith; Burge, Frederick I.; Flowerdew, Gordon; Cox, Jafna

    2004-01-01

    OBJECTIVE: Atrial fibrillation (AF) substantially increases risk of stroke. Evidence suggests that anticoagulation to reduce risk is underused (a "care gap"). Our objectives were to clarify measures of this gap in care by including data from family physicians and to determine why eligible patients were not receiving anticoagulation therapy. DESIGN: Telephone survey of family physicians regarding specific patients in their practices. SETTING: Nova Scotia. PARTICIPANTS: Ambulatory AF patients not taking warfarin who had risk factors that made anticoagulation appropriate. MAIN OUTCOME MEASURES: Proportion of patients removed from the care gap; reasons given for not giving the remainder anticoagulants. RESULTS: Half the patients thought to be in the care gap had previously unknown contraindications to anticoagulation, lacked a clear indication for anticoagulation, or were taking warfarin. Patients' refusal and anticipated problems with compliance and monitoring were among the reasons for not giving patients anticoagulants. CONCLUSION: Adding data from primary care physicians significantly narrowed the care gap. Attention should focus on the remaining reasons for not giving eligible patients anticoagulants. PMID:15508374

  7. Novel oral anticoagulants and their role in clinical practice.

    PubMed

    Wittkowsky, Ann K

    2011-12-01

    The complexities of oral anticoagulation with warfarin have led to the search for more practical alternative agents. Novel direct factor IIa inhibitors and direct factor Xa inhibitors currently in development can be administered at a fixed dose and do not require routine coagulation monitoring and ongoing dosage adjustment to ensure their effectiveness and safety. A number of phase III trials of these agents for the prevention of venous thromboembolism associated with orthopedic surgery and acute medical illness, for the treatment of venous thromboembolism, and for stroke prevention in patients with atrial fibrillation have been completed, with almost universally positive results. If these novel agents are approved for use in the United States, the future of oral anticoagulant therapy will allow a more nuanced approach to drug selection than has been available in the past. Attention to drug interactions and renal function will be required, as methods to measure the presence of these agents are not precise, cannot quantify the degree of anticoagulant present, and are influenced by the changes in serum drug concentrations during the dosing interval. In the future, patient preferences and the pharmacokinetic and pharmacodynamic characteristics of individual drugs will be able to be matched to optimize therapy. These new agents represent a new paradigm for anticoagulation that promises to improve patient care in the long term. PMID:22122180

  8. Anticoagulation in Pulmonary Arterial Hypertension.

    PubMed

    Robinson, Jeffrey C; Pugliese, Steven C; Fox, Daniel L; Badesch, David B

    2016-06-01

    Pulmonary arterial hypertension (PAH) is characterized by molecular and pathologic alteration to the pulmonary circulation, resulting in increased pulmonary vascular resistance, right ventricular failure, and eventual death. Pharmacologic treatment of PAH consists of use of a multitude of pulmonary vasodilators, sometimes in combination. PAH has been associated with increased thrombosis and disrupted coagulation and fibrinolysis, making anticoagulation an attractive and frequently employed therapeutic modality. Observational studies have provided some insight into the therapeutic potential of anticoagulation in idiopathic PAH, but there is a distinct lack of well-controlled prospective trials. Due to the conflicting evidence, there is a large amount of heterogeneity in the application of therapeutic anticoagulation in PAH and further well-controlled prospective trials are needed to clarify its role in treating PAH. PMID:27137522

  9. The novel anticoagulants: entering a new era.

    PubMed

    Bounameaux, H

    2009-02-01

    During the past five decades, anticoagulant therapy has consisted of rapidly acting parenteral drugs (unfractionated heparin [UFH] low-molecular-weight heparins [LMWH]) for prevention of venous thromboembolism and initial treatment of arterial and venous thromboembolism, whereas vitamin K antagonists (VKA) are used for longer term oral treatment. These drugs act by indirectly inhibiting several activated plasma clotting factors (UFH, LMWH) or by blocking the synthesis of some of them (VKA). In recent years, compounds that specifically block activated coagulation factor X (FXa) or thrombin have been developed. Thus, fondaparinux, and its long-acting derivative idraparinux, are administered subcutaneously. These substances inhibit F Xa indirectly via antithrombin. Small molecules have also been developed that directly block FXa (rivaroxaban, apixaban) or thrombin (dabigatran etexilate) following oral administration. In the present review we discuss the currently available evidence supporting the use of these new anticoagulants, in particular rivaroxaban and dabigatran etexilate, in the setting of thromboprophylaxis following major orthopaedic surgery, and the broader perspectives that these new drugs may open up in the next few years. PMID:19204837

  10. Anticoagulation in Atrial Fibrillation – Current Concepts

    PubMed Central

    Katritsis, Demosthenes G; Gersh, Bernard J; Camm, A John

    2015-01-01

    This article presents the current status of the use of anticoagulation for the treatment of AF, particularly with the use of non-vitamin K-dependent anticoagulants. Comparisons between these agents and warfarin are made and methods for assessment of anticoagulant activity and reversal are discussed. PMID:26835109

  11. Anticoagulation and delayed bowel resection in the management of mesenteric venous thrombosis

    PubMed Central

    Kim, Hyung-Kee; Chun, Jae Min; Huh, Seung

    2013-01-01

    Acute mesenteric venous thrombosis is potentially lethal because it can result in mesenteric ischemia and, ultimately, bowel infarction requiring surgical intervention. Systemic anticoagulation for the prevention of thrombus propagation is a well-recognized treatment modality and the current mainstay therapy for patients with acute mesenteric venous thrombosis. However, the decision between prompt surgical exploration vs conservative treatment with anticoagulation is somewhat difficult in patients with suspected bowel ischemia. Here we describe a patient with acute mesenteric venous thrombosis who presented with bowel ischemia and was treated with anticoagulation and delayed short-segment bowel resection. PMID:23946612

  12. Anticoagulation in Older Adults with Multimorbidity.

    PubMed

    Parks, Anna L; Fang, Margaret C

    2016-05-01

    The number of patients with atrial fibrillation (AF) who are of advanced age or have multiple comorbidities is expected to increase substantially. Older patients with AF generally gain a net benefit from anticoagulation. Guidelines typically recommend anticoagulation. There are multiple challenges in the safe use of anticoagulation in frail patients, including bleeding risk, monitoring and adherence, and polypharmacy. Although there are options for chronic oral anticoagulation, clinicians must understand the unique advantages and disadvantages of these medications when developing a management plan. This article reviews issues surrounding the appropriate use and selection of anticoagulants in complex older patients with AF. PMID:27113150

  13. Citrate anticoagulation for CRRT in children: comparison with heparin.

    PubMed

    Fernández, Sara Nicole; Santiago, Maria José; López-Herce, Jesús; García, Miriam; Del Castillo, Jimena; Alcaraz, Andrés José; Bellón, Jose María

    2014-01-01

    Regional anticoagulation with citrate is an alternative to heparin in continuous renal replacement therapies, which may prolong circuit lifetime and decrease hemorrhagic complications. A retrospective comparative cohort study based on a prospective observational registry was conducted including critically ill children undergoing CRRT. Efficacy, measured as circuit survival, and secondary effects of heparin and citrate were compared. 12 patients on CRRT with citrate anticoagulation and 24 patients with heparin anticoagulation were analyzed. Median citrate dose was 2.6 mmol/L. Median calcium dose was 0.16 mEq/kg/h. Median heparin dose was 15 UI/kg/h. Median circuit survival was 48 hours with citrate and 31 hours with heparin (P = 0.028). 66.6% of patients treated with citrate developed mild metabolic alkalosis, which was directly related to citrate dose. There were no cases of citrate intoxication: median total calcium/ionic calcium index (CaT/I) of 2.16 and a maximum CaT/I of 2.33, without metabolic acidosis. In the citrate group, 45.5% of patients developed hypochloremia and 27.3% hypomagnesemia. In the heparin group, 27.8% developed hypophosphatemia. Three patients were moved from heparin to citrate to control postoperatory bleeding. In conclusion citrate is a safe and effective anticoagulation method for CRRT in children and it achieves longer circuit survival than heparin. PMID:25157369

  14. Citrate Anticoagulation for CRRT in Children: Comparison with Heparin

    PubMed Central

    Fernández, Sara Nicole; Santiago, Maria José; López-Herce, Jesús; García, Miriam; Del Castillo, Jimena; Alcaraz, Andrés José; Bellón, Jose María

    2014-01-01

    Regional anticoagulation with citrate is an alternative to heparin in continuous renal replacement therapies, which may prolong circuit lifetime and decrease hemorrhagic complications. A retrospective comparative cohort study based on a prospective observational registry was conducted including critically ill children undergoing CRRT. Efficacy, measured as circuit survival, and secondary effects of heparin and citrate were compared. 12 patients on CRRT with citrate anticoagulation and 24 patients with heparin anticoagulation were analyzed. Median citrate dose was 2.6 mmol/L. Median calcium dose was 0.16 mEq/kg/h. Median heparin dose was 15 UI/kg/h. Median circuit survival was 48 hours with citrate and 31 hours with heparin (P = 0.028). 66.6% of patients treated with citrate developed mild metabolic alkalosis, which was directly related to citrate dose. There were no cases of citrate intoxication: median total calcium/ionic calcium index (CaT/I) of 2.16 and a maximum CaT/I of 2.33, without metabolic acidosis. In the citrate group, 45.5% of patients developed hypochloremia and 27.3% hypomagnesemia. In the heparin group, 27.8% developed hypophosphatemia. Three patients were moved from heparin to citrate to control postoperatory bleeding. In conclusion citrate is a safe and effective anticoagulation method for CRRT in children and it achieves longer circuit survival than heparin. PMID:25157369

  15. Contact laser prostatectomy in a patient on chronic anticoagulation

    NASA Astrophysics Data System (ADS)

    Mueller, Edward J.

    1995-05-01

    The `gold standard' therapy for patients with symptomatic bladder outlet obstruction secondary to benign prostatic hyperplasia has always been electrocautery TURP. However, in patients with medical problems requiring chronic anticoagulation, this procedure is contraindicated due to the extreme risk of hemorrhage, both during the procedure and the immediate post operative period. With the recent development of contact laser prostatectomy the patient on chronic anticoagulation can safely undergo the procedure. Herein, I present a case of a 60 year old with significant bladder outlet obstruction yielding an AUA symptom score of 18. The patient had a history of multiple episodes of deep venous thrombosis of the left leg with three prior pulmonary emboli. He was maintained on chronic anticoagulation with alternating days of 3.5 mg. and 5.0 mg. of warfarin sodium (coumadin). Preoperative cystoscopy showed a 4 cm prostatic fossa obstructed by tri-lobar hypertrophy, with large kissing lateral lobes and visual obstruction from the verumontanum. The patient underwent a contact laser prostatectomy with the SLT Nd:YAG laser at 50 watts. There was minimal bleeding both during the procedure and in the immediate postoperative period. At three months post-op the AUA symptom score had decreased to 2. This case demonstrated that contact laser prostatectomy can be safely and effectively performed in patients on chronic anticoagulation.

  16. Treatment of Venous Thromboembolism With New Anticoagulant Agents.

    PubMed

    Becattini, Cecilia; Agnelli, Giancarlo

    2016-04-26

    Venous thromboembolism (VTE) is a common disease associated with high risk for recurrences, death, and late sequelae, accounting for substantial health care costs. Anticoagulant agents are the mainstay of treatment for deep vein thrombosis and pulmonary embolism. The recent availability of oral anticoagulant agents that can be administered in fixed doses, without laboratory monitoring and dose adjustment, is a landmark change in the treatment of VTE. In Phase III trials, rivaroxaban, apixaban, edoxaban (antifactor Xa agents), and dabigatran (an antithrombin agent) were noninferior and probably safer than conventional anticoagulation therapy (low-molecular-weight heparin followed by vitamin K antagonists). These favorable results were confirmed in specific patient subgroups, such as the elderly and fragile. However, some patients, such as those with cancer or with intermediate- to high-risk pulmonary embolism, were underrepresented in the Phase III trials. Further clinical research is required before new oral anticoagulant agents can be considered standard of care for the full spectrum of patients with VTE. PMID:27102510

  17. 'Sailing in troubled waters': a review of the use of anticoagulation in adult cancer patients with thrombocytopenia.

    PubMed

    Ibrahim, Rami B; Skewes, Michelle D; Kuriakose, Philip

    2016-09-01

    Simply providing anticoagulation therapy is not as straightforward of a solution in cancer patients who have concurrent thrombocytopenia owing to the increased risk of bleeding complications. Currently, few guidelines are in place to assist clinicians in safely managing thrombocytopenic cancer patients on anticoagulation. The purpose of this review is to critically examine the available body of biomedical literature surrounding anticoagulant use against the backdrop of cancer-related thrombocytopenia in adult patients. Available evidence for the use of parenteral anticoagulants (low molecular weight heparins, unfractionated heparin, pentasaccharides, and direct thrombin inhibitors) and oral anticoagulants (vitamin K antagonists and novel oral anticoagulants) in thrombocytopenic cancer patients is described. The review revealed many inconsistencies between reports on this topic, which made it difficult to draw firm conclusions as to, for example, the ideal well tolerated anticoagulant dose in thrombocytopenic cancer patients? Intriguingly, critical clinical information including (but not limited) patient platelet nadirs, platelet counts during bleeding episodes, and platelet transfusion support was absent from a not-so-insignificant number of publications. Despite these shortcomings, the review sets out to formulate recommendations on the management of anticoagulation, at prophylactic or treatment doses, in adult cancer patients who also have concurrent thrombocytopenia. It also enlists a call for the medical community, by mapping select clinical guideposts, for further research in this setting. With the inclusion of these criteria in future studies, only then formal recommendations on the ideal safe dosage of anticoagulants in cancer patients, based on solid evidence, are conceived. PMID:26945262

  18. New oral anticoagulants: discussion on monitoring and adherence should start now!

    PubMed Central

    2013-01-01

    New oral anticoagulants (NOACs) have been introduced to improve anticoagulant therapy worldwide, but safe implementation may require additional measures. First, optimization of dose adjustment based on therapeutic levels of the drug may be more appropriate than fixed dose therapy. The development and implementation in quantitative laboratory assays will enable further dose optimization. Second, non-adherence to medication is a potential threat to the safe use of NOACs. Since cardiovascular medication may not be optimally used in about 50% of patients, procedures to improve adherence are imperative, also for NOAC therapy and in particular in elderly patients. PMID:23809888

  19. New anticoagulants - towards the development of an "ideal" anticoagulant.

    PubMed

    Haas, S

    2009-02-01

    Currently available anticoagulants, such as unfractionated heparin, low molecular weight heparins and vitamin K antagonists, have proved effective in the prevention and treatment of thromboembolic disorders. However, these drugs have some drawbacks, such as unpredictability (in the case of unfractionated heparin), non-specificity and parenteral mode of administration, which limit their use in the clinical setting. There is a need for new agents with efficacy similar to that of these classes of anticoagulants and none of their associated drawbacks. Advances are being made in the development of more convenient and more specific drugs, with the aim to improve substantially the prevention and management of thromboembolic disorders. This review will emphasize how the development of an ideal anticoagulant, with potential benefits including high efficacy, safety, low levels of bleeding, fixed dosing, rapid onset of action, ability to bind clot-bound coagulation factors and no requirement for therapeutic monitoring, is a considerable challenge. This review will present the most relevant preclinical data, as well as the clinical studies performed to date, for several drug classes. Direct thrombin inhibitors, such as dabigatran etexilate, will be reviewed, as well as indirect (fondaparinux and idraparinux) and direct (rivaroxaban, apixaban, among others) Factor Xa inhibitors, Factor IXa inhibitors and monoclonal antibodies against Factor IX/IXa. PMID:19229800

  20. Atrial sensor, remote monitoring and new anticoagulant drugs: Identification and treatment of a patient with unknown and asymptomatic atrial flutter

    PubMed Central

    Quartieri, Fabio; Giacopelli, Daniele; Iori, Matteo; Bottoni, Nicola

    2015-01-01

    This case report describes how new tools and technologies can drive a different approach in the management of arrhythmic patients. An unknown and asymptomatic atrial flutter was detected by the atrial sensor mounted in a single lead implantable cardioverter defibrillator. Moreover daily remote monitoring of the device allowed early notification and prompt clinical reaction. Anticoagulant therapy onset, radiofrequency ablation and the following anticoagulant therapy removal were driven by the device data transmissions. PMID:26937114

  1. Reversal of novel oral anticoagulants.

    PubMed

    Abo-Salem, Elsayed; Becker, Richard C

    2016-04-01

    The development of a new generation of non-vitamin K oral anticoagulants represents a potential breakthrough in the management of patients with thrombotic diseases, disorders and conditions. While a large and growing body of evidence from large-scale clinical trials and registries supports a favorable safety profile, having a means to rapidly reverse their anticoagulant effects represents an unmet need among practicing clinicians. Several targeted reversal agents are currently in development and the early results are promising. Idarucizumab is a monoclonal antibody that can immediately and specifically reverse dabigatran. Andexanet alfa is a recombinant modified factor Xa that can bind and reverse oral and parenteral factor Xa inhibitors, including rivaroxaban, apixaban and edoxaban, and low molecular weight heparin. Aripazine is a small molecule that can reverse the action of factor Xa inhibitors and possibly dabigatran as well through non-covalent binding and charge-charge interactions. PMID:26939028

  2. The challenges of lupus anticoagulants.

    PubMed

    Chighizola, Cecilia Beatrice; Raschi, Elena; Banzato, Alessandra; Borghi, Maria Orietta; Pengo, Vittorio; Meroni, Pier Luigi

    2016-01-01

    The term "lupus anticoagulant" (LA) refers to a heterogeneous group of immunoglobulins behaving as acquired in vitro inhibitors of coagulation. These antibodies, namely anti-β2GPI and anti-prothrombin antibodies, induce the in vitro elongation of clotting time interfering with phospholipid-dependent coagulation cofactors. Positive LA is associated with thrombosis and pregnancy complications, providing one of the three laboratory criteria for the classification of the anti-phospholipid syndrome. LA is the strongest predictor of clinical events, especially when associated with other anti-phospholipid antibodies. Much more controversial is the risk conveyed by isolated and weak LA. LA detection is technically laborious, envisaging screening, mixing and confirming tests. Hopefully critical issues in LA detection, such as the interference of anticoagulants, will be overcome, in the next future. PMID:26789237

  3. Assessing Anticoagulation Practice Patterns in Patients on Durable Mechanical Circulatory Support Devices: An International Survey.

    PubMed

    Jennings, Douglas L; Horn, Edward T; Lyster, Haifa; Panos, Anthony L; Teuteberg, Jeffrey J; Lehmkuhl, Hans B; Perez, Alexandra; Shullo, Michael A

    2016-01-01

    Anticoagulation in mechanical circulatory support (MCS) patients dictated by local practice, and therefore uniform standards for management are lacking. To characterize the worldwide variance in anticoagulation and antiplatelet therapy in patients with MCS devices, a 42 item survey was created and distributed electronically in August 2014. The survey assessed the center-perceived thromboembolic risk (minimal, low, moderate, or high) and characterized the antiplatelet and anticoagulant strategies for the Thoratec HeartMate II (HMII) and HeartWare HVAD (HVAD). A total of 83/214 centers (39%) responded: North America (60/152), Europe (18/50), Australia (2/4), and Asia (3/8). Although the most common target international normalized ratio (INR) was 2-3 for both devices, significant variability exists. Anticoagulation intensity tended to be lower with the HMII, with more centers targeting INR values of less than 2.5. Aspirin monotherapy was the most common antiplatelet regimen; however, the HVAD patients were more likely to be on daily aspirin doses over 100 mg. In addition, parenteral bridging was more frequent with the HVAD device. While 43.8% of respondents indicated an increase in the perceived risk of HMII device thrombosis in 2014, intensification of anticoagulation (22%) or antiplatelet (11%) therapy was infrequent. Our findings verify the wide variety of anticoagulation practice patterns between MCS centers. PMID:26309097

  4. Oral anticoagulation with Factor Xa and thrombin inhibitors: Is there an alternative to warfarin?

    PubMed

    Zikria, Jennifer; Ansell, Jack

    2009-12-01

    Vitamin K antagonists (VKA), such as warfarin, have been the only available oral anticoagulants despite their many limitations. The greatest medical need is to find a replacement for warfarin for long-term therapy, particularly for stroke prevention in atrial fibrillation (AF) patients. Emerging oral anticoagulants are free from many of warfarin's drawbacks and may offer a convenient alternative. Drugs in advanced development target factor Xa (rivaroxaban, apixaban) or thrombin (dabigatran etexilate). Recently, the RE-LY phase III study found dabigatran etexilate was an effective and convenient alternative to warfarin in stroke prevention for AF patients. Within the next two years, similar studies comparing rivaroxaban and apixaban versus warfarin in AF patients will become available. This paper reviews warfarin's limitations, discusses the pharmacokinetics of emerging anticoagulants in advanced development, and summarizes trials with an emphasis on head-to-head studies comparing novel anticoagulants to warfarin. PMID:20040270

  5. Electrochemical assay of heparin to monitor anticoagulation action in cardiovascular patients.

    PubMed

    Singh, Niyati

    2012-06-01

    Complications in anticoagulation therapy and long term consequences of the post thrombotic syndromes requires a fast and powerful therapy such as heparin therapy (anticoagulation) to minimize the thrombotic effects in patients. Thus, a simple approach via electrochemical method: Differential pulse polarography (DPP) has been developed for heparin analysis as a powerful clinical tool to monitor anticoagulation action in-patient undergoing heparin therapy. The method has been standardized for determination of heparin activity over the existing methods and a very well defined characteristic reduction peak at -1.25 V in 2 M NaOH was observed for heparin. A linear relation was observed with a regression equation as y = 0.3117x + 0.8069, for 0.1 to 2.0 units/ml heparin. The developed DPP method was observed with excellent precision, accuracy and recovery in human blood plasma samples and in pharmacological formulations. The limit of detection (LOD) and limit of quantification (LOQ) noticed to be 2.04 and 6.8 units/ml respectively. The DPP results compared with pharmacological screening through average thrombin time (TT) and applied to monitor invitro anticoagulation action of heparin in healthy human subjects. Statistical analysis done to validate developed DPP method for heparin analysis and its probable clinical use to monitor anticoagulation action to treat patients suffering from various cerebrovascular disorders (CVD) by proper dosing of heparin. PMID:23730016

  6. Coagulation assessment with the new generation of oral anticoagulants

    PubMed Central

    Pollack, Charles V

    2016-01-01

    Long-term oral anticoagulant (OAC) therapy is used for the treatment and prevention of thrombosis and thromboembolism. As OAC use is so widespread, emergency physicians are likely to encounter patients on anticoagulant therapy in the emergency department (ED) on a regular basis, either for the same reasons as the population in general or as a result of the increased bleeding risk that OAC use entails. The vitamin K antagonist warfarin has been the standard OAC for several decades, but recently, the newer agents dabigatran etexilate, rivaroxaban and apixaban (collectively, novel OACs, non-vitamin K OACs, or simply ‘NOACs’) have become available for long-term use. Protocols for assessing and managing warfarin-treated patients in the ED are well established and include international normalised ratio (INR) testing, which helps guide patient management. However, the INR does not give an accurate evaluation of coagulation status with NOACs, and alternative tests are therefore needed for use in emergency settings. This paper discusses what information the INR provides for a patient taking warfarin and which coagulation tests can guide the physician when treating patients on one of the NOACs, as well as other differences in emergency anticoagulation management. PMID:25987596

  7. Coagulation assessment with the new generation of oral anticoagulants.

    PubMed

    Pollack, Charles V

    2016-06-01

    Long-term oral anticoagulant (OAC) therapy is used for the treatment and prevention of thrombosis and thromboembolism. As OAC use is so widespread, emergency physicians are likely to encounter patients on anticoagulant therapy in the emergency department (ED) on a regular basis, either for the same reasons as the population in general or as a result of the increased bleeding risk that OAC use entails.The vitamin K antagonist warfarin has been the standard OAC for several decades, but recently, the newer agents dabigatran etexilate, rivaroxaban and apixaban (collectively, novel OACs, non-vitamin K OACs, or simply 'NOACs') have become available for long-term use. Protocols for assessing and managing warfarin-treated patients in the ED are well established and include international normalised ratio (INR) testing, which helps guide patient management. However, the INR does not give an accurate evaluation of coagulation status with NOACs, and alternative tests are therefore needed for use in emergency settings. This paper discusses what information the INR provides for a patient taking warfarin and which coagulation tests can guide the physician when treating patients on one of the NOACs, as well as other differences in emergency anticoagulation management. PMID:25987596

  8. A Comprehensive Overview of Direct Oral Anticoagulants for the Management of Venous Thromboembolism.

    PubMed

    Comerota, Anthony J; Ramacciotti, Eduardo

    2016-07-01

    Venous thromboembolism (VTE) is a prevalent, potentially fatal health problem. Although standard anticoagulant therapy is effective when compared with the newer direct oral anticoagulants (DOACs), it has disadvantages. Heparin and its derivatives must be administered parenterally, whereas use of oral vitamin K antagonists is complicated by unpredictable pharmacokinetics and pharmacodynamics, drug-food and drug-drug interactions and the requirement for frequent laboratory monitoring. Randomized phase 3 trials have demonstrated that patients receive similarly effective anticoagulation with the DOACs dabigatran, edoxaban, rivaroxaban and apixaban when compared with warfarin, with similar or reduced risk of bleeding. Extended therapy trials have consistently demonstrated superior effectiveness for DOAC treatment when compared with placebo in preventing VTE recurrence. This article presents a comprehensive review of the pharmacokinetics, pharmacodynamics and accumulated clinical trial evidence for each DOAC for short-term, long-term and extended VTE therapy, and it considers the potential implications these agents have for the clinical management of VTE. PMID:27432042

  9. Direct oral anticoagulants and venous thromboembolism.

    PubMed

    Franchini, Massimo; Mannucci, Pier Mannuccio

    2016-09-01

    Venous thromboembolism (VTE), consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban) and thrombin inhibitors (e.g. dabigatran etexilate). This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE. PMID:27581829

  10. Secondary poisoning of owls by anticoagulant rodenticides

    USGS Publications Warehouse

    Mendenhall, V.M.; Pank, L.F.

    1980-01-01

    Anticoagulants-compounds that prevent clotting of the blood-are extensively used for control of small mammal pests. The potential secondary hazards of 6 anticoagulant rodenticides to birds of prey were examined in this study. Whole rats or mice were killed with each anticoagulant and were fed to 1-3 species of owls. Owls died of hemorrhaging after feeding on rats killed with bromadiolone, brodifacoum, or diphacinone; sublethal hemorrhaging occurred in owls fed rats killed with difenacoum. These results demonstrate potential secondary hazards of 4 anticoagulants to avian predators. No abnormalities were observed in owls fed rats killed with fumarin and chlorophacinone

  11. Novel Anticoagulants in Atrial Fibrillation: Monitoring, Reversal and Perioperative Management

    PubMed Central

    Shamoun, Fadi; Obeid, Hiba; Ramakrishna, Harish

    2015-01-01

    Atrial fibrillation continues to be a significant source of morbidity and mortality worldwide. Effective anticoagulation remains the cornerstone of outpatient and inpatient treatment. The use of the new generation of anticoagulants (NOACs) continues to grow. Recently published data indicate their cost-effectiveness and overall safety in stroke prevention; compared to vitamin K antagonists, they can be prescribed in fixed doses for long-term therapy without the need for coagulation monitoring. Both United States and European Guidelines recommend NOACs for stroke prevention in patients with atrial fibrillation. This review discusses each of the NOACs, along with their efficacy and safety data. It explores the most recent guidelines regarding their perioperative use in atrial fibrillation patients. It also discusses bleeding complications, perioperative management, and reversal agents. PMID:26221593

  12. Delayed intra-abdominal bleeding following trans-vaginal ultrasonography guided oocyte retrieval for in vitro fertilization in patients at risk for thrombo-embolic events under anticoagulant therapy

    PubMed Central

    Orvieto, Raoul

    2013-01-01

    We report herein, two cases of massive delayed (2 and 4 days) intra abdominal hemorrhage following ovum pick-up (OPU), in patients at risk for thrombo-embolic events, who concomitantly used therapeutic doses of low molecular weight heparin (LMWH). We discuss the possible mechanisms involved in causing the aforementioned delayed bleeding, and call for re-evaluation of the presently accepted anticoagulant co-treatment regimen. These case reports should direct physicians' attention and keep them alert, while conducting IVF treatment to this subgroup of high risk patients. PMID:24555090

  13. Differential In Vitro Inhibition of Thrombin Generation by Anticoagulant Drugs in Plasma from Patients with Cirrhosis

    PubMed Central

    Potze, Wilma; Arshad, Freeha; Adelmeijer, Jelle; Blokzijl, Hans; van den Berg, Arie P.; Meijers, Joost C. M.; Porte, Robert J.; Lisman, Ton

    2014-01-01

    Background Treatment and prevention of thrombotic complications is frequently required in patients with cirrhosis. However anticoagulant therapy is often withheld from these patients, because of the perceived bleeding diathesis. As a result of the limited clinical experience, the anticoagulant of choice for the various indications is still not known. Objectives We evaluated the in vitro effect of clinically approved anticoagulant drugs in plasma from patients with cirrhosis. Patients/Methods Thirty patients with cirrhosis and thirty healthy controls were studied. Thrombin generation assays were performed before and after addition of unfractionated heparin, low molecular weight heparin, fondaparinux, dabigatran, and rivaroxaban, to estimate anticoagulant potencies of these drugs. Results Addition of dabigatran led to a much more pronounced reduction in endogenous thrombin potential in patients compared to controls (72.6% reduction in patients vs. 12.8% reduction in controls, P<0.0001). The enhanced effect of dabigatran was proportional to the severity of disease. In contrast, only a slightly increased anticoagulant response to heparin and low molecular weight heparin and even a reduced response to fondaparinux and rivaroxaban was observed in plasma from cirrhotic patients as compared to control plasma. Conclusions The anticoagulant potency of clinically approved drugs differs substantially between patients with cirrhosis and healthy individuals. Whereas dabigatran and, to a lesser extent, heparin and low molecular weight heparin are more potent in plasma from patients with cirrhosis, fondaparinux and rivaroxaban showed a decreased anticoagulant effect. These results may imply that in addition to dose adjustments based on altered pharmacokinetics, drug-specific dose adjustments based on altered anticoagulant potency may be required in patients with cirrhosis. PMID:24505487

  14. Telephone-based anticoagulation management in the homebound setting: a retrospective observational study

    PubMed Central

    Hassan, Samer; Naboush, Ali; Radbel, Jared; Asaad, Razan; Alkaied, Homam; Demissie, Seleshi; Terjanian, Terenig

    2013-01-01

    Background Anticoagulation management is currently performed through anticoagulation clinics or self-managed with or without the help of medical services. Homebound patients are a unique population that cannot utilize anticoagulation clinics or self-testing. Telephone-based anticoagulation management could be an alternative to the traditional methods of monitoring warfarin in this subgroup. The objective of this retrospective, observational study is to investigate the feasibility of warfarin management in homebound patients. Methods This study was performed through the use of telephone-based adjustments of warfarin dose based on an international normalized ratio (INR) result. Four hundred forty-eight homebound patients referred to the anticoagulation clinic at Staten Island University Hospital were visited at home by a phlebotomist; a blood sample was drawn for initial laboratory testing. A nurse practitioner then called the patient or designated person to relay the INR result and to direct dosage adjustment. INR results and dosage changes were entered into an electronic medical record and analyzed statistically. Results The mean percentage of INR values in range was 58.39%. The mean time when the INR was in the therapeutic range was 62.75%. The percent of patients who were therapeutically controlled decreased as the number of medications increased. The complication rate was 4% per patient year, with an equal distribution between bleeding and clotting. These values compared favorably to other studies in which monitoring was performed through anticoagulation clinics or self-monitoring. The cost per visit at our anticoagulation clinic was found to be approximately $300 compared with $82 when utilizing our homebound service. Conclusion Telephone-based management of warfarin therapy in the homebound setting is feasible. It can lower the cost of health care expenditures compared to other modalities of anticoagulation management. PMID:24348065

  15. Use of novel oral anticoagulants for patients with atrial fibrillation: systematic review and clinical implications.

    PubMed

    Albert, Nancy M

    2014-01-01

    Atrial fibrillation (AF), a common arrhythmia, increases the risk of ischemic stroke. Stroke and bleeding scores for patients with AF can help to stratify risk and determine the need for antithrombotic therapy, for which warfarin has been the gold standard. Although highly effective, warfarin has several limitations that can lead to its underuse. Data from randomized, Phase III clinical trials of the novel oral anticoagulants, dabigatran, a direct thrombin inhibitor, and rivaroxaban and apixaban, both factor Xa inhibitors, indicate these drugs are at least noninferior to warfarin for the prevention of stroke and systemic embolism. They are easier to administer, and have an equivalent or lower risk of bleeding versus warfarin. A better understanding of the risks and benefits of the novel oral anticoagulants, and their use in clinical practice, will prepare clinicians to anticipate and address educational and clinical needs of AF patients and their families, and promote evidence-based prescription of appropriate and safe anticoagulation therapy. PMID:24373340

  16. Pharmacogenetics of antiplatelets and anticoagulants: a report on clopidogrel, warfarin and dabigatran.

    PubMed

    Ross, Stephanie; Paré, Guillaume

    2013-10-01

    Genetic polymorphisms are thought to contribute to the wide intraindividual variability in antiplatelet and anticoagulant drug response. Pharmacogenetics is the study of how genetic variants influence drug response and how the adoption of a more personalized approach in antiplatelet and anticoagulant therapy may help to minimize harmful drug effects and optimize care for individual patients. However, due to sometimes conflicting evidence, the uptake of pharmacogenetics in the clinical setting has been slow. In this article, we review the genetic mechanisms contributing to the variability in response to three commonly used and emerging antiplatelet and anticoagulant drug therapies, namely clopidogrel, warfarin and dabigatran. We will focus on common genetic variants that influence the absorption, metabolism and/or action of these agents, including CYP2C19 (*2, *3 and *17), CYP3A4, CYP3A5, CYP2C9, ABCB1, P2RY12, CYP2C9 (*2/*3), VKORC1 and CESI. PMID:24088127

  17. Should patients with systemic sclerosis-related pulmonary arterial hypertension be anticoagulated?

    PubMed

    Nikpour, M; Stevens, W; Proudman, S M; Buchbinder, R; Prior, D; Zochling, J; Williams, T; Gabbay, E; Nandurkar, H

    2013-05-01

    Pulmonary arterial hypertension (PAH) is a major cause of mortality in scleroderma and despite 'advanced' therapies confers a median survival of less than 5 years. Anticoagulation in systemic sclerosis-related PAH (SSc-PAH) is currently one of the most contentious issues in the management of patients with connective tissue disease. While some studies have shown a survival benefit with warfarin therapy in this disease, others have not. Accordingly, a state of clinical equipoise exists in relation to anticoagulation in SSc-PAH. With an over fivefold reduction in mortality demonstrated in some observational studies, the issue of anticoagulation in SSc-PAH demands resolution through a well-designed randomised controlled trial. PMID:23668273

  18. Novel oral Anticoagulants in Non-Valvular Atrial Fibrillation

    PubMed Central

    da Silva, Rose M.F.L.

    2014-01-01

    Atrial fibrillation is the most frequent arrhythmia in clinical practice, reaching 2% of the people in the world and is associated with systemic embolism. Thus, the use of anticoagulants is indicated if CHA2DS2-VASc score ≥2 or in patients with previous transient ischemic attack or stroke. For decades, warfarin, a vitamin K antagonist, was the only choice for chronic oral anticoagulation. Recently, novel oral anticoagulants (NOACs) have been introduced, offering similar (or better) effectiveness, safety, and convenience to the vitamin K antagonists. Dabigatran was the first NOAC approved and is a direct thrombin inhibitor. Rivaroxaban and apixaban are factor Xa inhibitors. They display rapid onset of action, more predictable of pharmacological profile, less interactions with other drugs, lack of significant effects in the diet, and less risk of intracranial hemorrhage than warfarin. Despite that dose adjustment is necessary for patients with chronic kidney disease or according to body weight, these new drugs do not require regular monitoring. There are recommendations for the start and follow-up therapy with NOACs, planning for cardioversion, ablation and surgical interventions and the management of bleeding. This article is a review of the major studies of the NOACs. The clinical use of these drugs in patients with non-valvular atrial fibrillation is presented. PMID:25470147

  19. Safety of new oral anticoagulant drugs: a perspective

    PubMed Central

    Vílchez, Juan Antonio; Gallego, Pilar

    2014-01-01

    The recent development of new oral anticoagulants (NOACs) offers the possibility of efficacy, relative safety and convenience compared with warfarin. This could lead to greater patient compliance, with easier management and improved provision of thromboprophylaxis. Safety whilst using NOACs should be focused on bleeding cases, surgery or on the management of patients receiving anticoagulant therapy with concomitant impairment of renal function, especially since many NOACs are dependent on renal excretion. Thus, if the clearance creatinine indicates severe renal impairment, NOACS will be contraindicated or their dose needs to be changed. In patients who need surgery, there are published protocols of management, depending on the severity of the intervention and renal function. In the case of severe hemorrhage, requiring rapid reversal of the anticoagulant effect and in the absence of specific antidotes, alternatives such as one of the nonspecific haemostatic agents must be considered. Clinical evaluation in bleeding situations and a meticulous risk–benefit appraisal for NOACs is needed, and these procoagulant agents and patients must be monitored closely. This article provides an overview of the pharmacology and potential risks, as well as the efficacy and safety of NOACs. PMID:25083259

  20. Novel oral anticoagulants for heparin-induced thrombocytopenia.

    PubMed

    Skelley, Jessica W; Kyle, Jeffrey A; Roberts, Rachel A

    2016-08-01

    To review the use of the novel oral anticoagulant (NOAC) agents for the treatment of heparin-induced thrombocytopenia (HIT) from relevant clinical trial data. A MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google-Scholar searches (1966-March 2016) were conducted using the keywords: thrombocytopenia, NOACs, dabigatran, apixaban, rivaroxaban, edoxaban, Xa inhibitor, direct thrombin inhibitor. Articles evaluating the new oral anticoagulants for thrombocytopenia published in English and using human subjects were selected. Eight clinical trials were identified. References cited in identified articles were used for additional citations. Approximately 12 million hospitalized patients each year are exposed to heparin for thromboprophylaxis. HIT, an immune-mediated, prothrombotic adverse reaction is a potential complication of heparin therapy. As a result, heparin products must be immediately withdrawn and replaced by alternative anticoagulants to compensate for the thrombotic risk associated with HIT. Limitations exist with the only currently FDA approved heparin alternative, argatroban. NOACs have been considered as potential alternatives to traditional agents based on their pharmacologic activity. Case reports have indicated positive results in patients, with clinical outcomes and tolerability supporting the use of the NOACs as alternative agents in the treatment of HIT. Positive results have been reported for the use of NOACs in the treatment of HIT. Further robust studies are needed for definitive decision making by clinicians. PMID:27102287

  1. Anticoagulants

    MedlinePlus

    ... or interactions with other medicines and vitamin or herbal supplements. This information should not be used as medical ... your doctor about every medicine and vitamin or herbal supplement that you are taking, so he or she ...

  2. Anticoagulation

    MedlinePlus

    ... gums or nosebleeds. Oral Medications These mainly include aspirin or clopidogrel (Plavix) and warfarin (Coumadin). These medications ... will decide which one is right for you. Aspirin tends to cause fewer bleeding complications than clopidogrel ...

  3. Development and implementation of a pharmacist-managed inpatient anticoagulation monitoring program.

    PubMed

    Wellman, Jessica C; Kraus, Peggy S; Burton, Bradley L; Ensor, Christopher R; Nesbit, Todd W; Ross, Patricia A; Thomas, Michelle L; Streiff, Michael B

    2011-05-15

    PURPOSE. A stepwise approach to development and implementation of a program to standardize and increase pharmacists' involvement in anticoagulation therapy at a large academic medical center is described. SUMMARY. In response to the Joint Commission's national goal of improved patient safety in anticoagulation therapy, a work group of pharmacy administrators, educators, clinical specialists, and decentralized pharmacists at the hospital developed the structure for a comprehensive inpatient anticoagulation program (IAP); the work group also developed a list of required competencies, educational materials, assessment methods, and mechanisms for eliciting feedback from IAP pharmacists and other patient care staff. After completion of training that included structured case-review sessions, a one-on-one shadowing experience, and competency assessment, IAP pharmacists began reviewing clinical and laboratory data on patients receiving warfarin and low-molecular-weight heparins and providing recommendations to physicians, nurse practitioners, and other health care team members. Feedback from other clinicians was generally positive, with a majority of those surveyed indicating that increased pharmacist involvement in anticoagulation monitoring and dosage adjustment resulted in improved patient care; about 80% indicated that they concurred with pharmacists' recommendations at least 75% of the time. Results of a survey of IAP pharmacists indicated increased satisfaction with their daily duties but also a need for improved pharmacist-to-pharmacist communication. CONCLUSION. Case-based advanced training and implementation of an IAP in a tertiary care hospital increased pharmacists' involvement in the management of inpatients receiving anticoagulants. PMID:21546645

  4. Gastrointestinal Bleeding and Anticoagulant or Antiplatelet Drugs: Systematic Search for Clinical Practice Guidelines

    PubMed Central

    Gutermann, Irit Kaye; Niggemeier, Verena; Zimmerli, Lukas U.; Holzer, Barbara M.; Battegay, Edouard; Scharl, Michael

    2015-01-01

    Abstract Gastrointestinal (GI) bleeding is a frequently encountered and very serious problem in emergency room patients who are currently being treated with anticoagulant or antiplatelet medications. There is, however, a lack of clinical practice guidelines about how to respond to these situations. The goal of this study was to find published articles that contain specific information about how to safely adjust anticoagulant and antiplatelet therapy when GI bleeding occurs. The investigators initiated a global search on the PubMed and Google websites for published information about GI bleeding in the presence of anticoagulant or antiplatelet therapy. After eliminating duplicate entries, the medical articles that remained were screened to narrow the sets of articles to those that met specific criteria. Articles that most closely matched study criteria were analyzed in detail and compared to determine how many actual guidelines exist and are useful. We could provide only minimal information about appropriate therapeutic strategies because no articles provided sufficient specific advice about how to respond to situations involving acute GI bleeding and concurrent use of anticoagulant or antiplatelet drugs. Only 4 articles provided enough detail to be of any use in an emergency situation. Clinical practice guidelines and also clinical trials for GI hemorrhaging should be expanded to state in which situations the use of anticoagulant or antiplatelet drugs should be suspended and the medications should later be resumed, and they should state the level of risk for any particular action. PMID:25569664

  5. Direct oral anticoagulants: key considerations for use to prevent stroke in patients with nonvalvular atrial fibrillation

    PubMed Central

    Ment, Jerome

    2015-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Strokes that occur as a complication of AF are usually more severe and associated with a higher disability or morbidity and mortality rate compared with non-AF-related strokes. The risk of stroke in AF is dependent on several risk factors; AF itself acts as an independent risk factor for stroke. The combination of effective anticoagulation therapy, risk stratification (based on stroke risk scores, such as CHADS2 and CHA2DS2-VASc), and recommendations provided by guidelines is essential for decreasing the risk of stroke in patients with AF. Although effective in preventing the occurrence of stroke, vitamin K antagonists (VKAs; eg, warfarin) are associated with several limitations. Therefore, direct oral anticoagulants, such as apixaban, dabigatran etexilate, edoxaban, and rivaroxaban, have emerged as an alternative to the VKAs for stroke prevention in patients with nonvalvular AF. Compared with the VKAs, these agents have more favorable pharmacological characteristics and, unlike the VKAs, they are given at fixed doses without the need for routine coagulation monitoring. It remains important that physicians use these direct oral anticoagulants responsibly to ensure optimal safety and effectiveness. This article provides an overview of the existing data on the direct oral anticoagulants, focusing on management protocols for aiding physicians to optimize anticoagulant therapy in patients with nonvalvular AF, particularly in special patient populations (eg, those with renal impairment) and other specific clinical situations. PMID:26089678

  6. Use of the activated clotting time in anticoagulation monitoring of intravascular procedures.

    PubMed Central

    Bowers, J; Ferguson, J J

    1993-01-01

    The activated clotting time first came into clinical use in the mid-1970s to guide the administration and reversal of heparin during cardiopulmonary bypass procedures. The explosive growth of cardiopulmonary bypass led to the development of automated techniques for measuring activated clotting times. Recent advances in the field of interventional cardiology have emphasized the importance of the coagulation cascade and the need for the prevention of thrombosis with anticoagulant drugs. The activated clotting time has emerged as an important means of monitoring and guiding heparin therapy during invasive intravascular procedures. This review focuses on the following topics: 1) the development of anticoagulation monitoring techniques; 2) current alternatives in bedside anticoagulation monitoring; and 3) the clinical application of activated clotting times outside surgery. Until prospective studies can establish appropriate "target" activated-clotting-time values for interventional procedures, procedural anticoagulation must be guided empirically. Nevertheless, the activated clotting time is extremely useful in the catheterization laboratory, for monitoring heparin therapy and the adequacy of anticoagulation. PMID:8298321

  7. Adherence to long-term anticoagulation treatment, what is known and what the future might hold.

    PubMed

    Abdou, John K; Auyeung, Vivian; Patel, Jignesh P; Arya, Roopen

    2016-07-01

    Adherence to medication, commonly reported as being 50% in chronic diseases, is of great concern in healthcare. Medication non-adherence is particularly apparent in chronic diseases, where treatment is often preventative and may provide little or no symptomatic relief or feedback for the patient. A lot of research has been undertaken to describe the extent of non-adherence to long-term anticoagulation therapy, particularly with vitamin K antagonists and more recently with direct oral anticoagulants. However, the literature is scarce with respect to describing adherence to anticoagulation in terms of the behavioural aspects that influence medicine use. Utilizing the COM-B (capability, opportunity, motivation and behaviour) psychological model of non-adherence, we present the available evidence, not only in terms of describing the extent of the non-adherence problem, but also describing why patients do not adhere, offering theory-driven and evidence-based solutions to improve long-term adherence to chronic anticoagulation therapy. Lessons learned are not only applicable within the field of anticoagulation but throughout haematology. PMID:27173746

  8. A Summary of the Literature Evaluating Adherence and Persistence with Oral Anticoagulants in Atrial Fibrillation.

    PubMed

    Obamiro, Kehinde O; Chalmers, Leanne; Bereznicki, Luke R E

    2016-10-01

    Atrial fibrillation (AF) is a growing public health concern and remains an independent risk factor for ischemic stroke. Warfarin, a commonly used oral anticoagulant, is associated with a 60-70 % relative reduction in stroke risk and a reduction in mortality of 26 %. However, warfarin has several limitations, including a narrow therapeutic window, variable dose response, multiple interactions with other drugs and concurrent illnesses, and the need for frequent laboratory monitoring. In recent years, the direct acting oral anticoagulants (DOACs), including dabigatran, rivaroxaban, apixaban and edoxaban, have been developed to overcome the limitations of warfarin therapy. These treatment strategies are either comparable or superior to warfarin in stroke prevention in AF. Despite the documented effectiveness of oral anticoagulants in AF, patients may not derive optimal benefit if they fail to adhere or fail to continue with their medication. This may lead to treatment failure, increased hospitalization and mortality. This review summarizes the literature regarding adherence and persistence (or discontinuation) rates with oral anticoagulants in the management of AF; the impact of non-adherence and non-persistence on treatment outcomes; and the effectiveness of strategies to improve adherence and persistence with oral anticoagulant therapy. PMID:27262433

  9. Self-Titrating Anticoagulant Nanocomplexes That Restore Homeostatic Regulation of the Coagulation Cascade

    PubMed Central

    2015-01-01

    Antithrombotic therapy is a critical portion of the treatment regime for a number of life-threatening conditions, including cardiovascular disease, stroke, and cancer; yet, proper clinical management of anticoagulation remains a challenge because existing agents increase the propensity for bleeding in patients. Here, we describe the development of a bioresponsive peptide–polysaccharide nanocomplex that utilizes a negative feedback mechanism to self-titrate the release of anticoagulant in response to varying levels of coagulation activity. This nanoscale self-titrating activatable therapeutic, or nanoSTAT, consists of a cationic thrombin-cleavable peptide and heparin, an anionic polysaccharide and widely used clinical anticoagulant. Under nonthrombotic conditions, nanoSTATs circulate inactively, neither releasing anticoagulant nor significantly prolonging bleeding time. However, in response to life-threatening pulmonary embolism, nanoSTATs locally release their drug payload and prevent thrombosis. This autonomous negative feedback regulator may improve antithrombotic therapy by increasing the therapeutic window and decreasing the bleeding risk of anticoagulants. PMID:25119520

  10. Effective reversal of warfarin-induced excessive anticoagulation with low dose vitamin K1.

    PubMed

    Shetty, H G; Backhouse, G; Bentley, D P; Routledge, P A

    1992-01-23

    Reversal of the anticoagulant effect of warfarin in patients with no active haemorrhage can be achieved by administration of intravenous vitamin K1. Currently recommended doses of intravenous vitamin K1, for this purpose often result in subsequent difficulties in anticoagulation. We observed the response to low dose intravenous vitamin K1 in patients requiring reversal of anticoagulant therapy. Ten consecutive patients received 1 mg and 21 further patients received 0.5 mg of intravenous vitamin K1. In 50% of the patients who received 1 mg of vitamin K1 the INR (International Normalised Ratio) fell below 2 at 24 h whereas in patients who received 0.5 mg the INR fell below 5.5 in all subjects after 24 h and in none did it fall below 2.0. No patient had any thrombotic or haemorrhagic complications and no difficulty was encountered in re-establishing anticoagulant control after 24 h. We recommend 0.5 mg of vitamin K1 as an effective and convenient method of predictable and fine control of oral anticoagulant therapy. PMID:1615468

  11. [New oral anticoagulants (NOAC) in nephrology].

    PubMed

    Bellasi, Antonio; Di Lullo, Luca; Melfa, Gianvincenzo; Minoretti, Claudio; Ratti, Carlo; Campana, Carlo; Volpi, Maurizio; Mangano, Stefano; Di Iorio, Biagio; Cozzolino, Mario

    2016-01-01

    The new or direct oral anticoagulants [new oral anticoagulants (NOAC) or direct oral anticoagulants (DOAC)] were launched in the Italian market in 2013. Although these compounds share common pharmacological indications with vitamin K antagonists (warfarin or acenocumarol), they have different mechanisms of action, do not require a constant anticoagulant monitoring but are more efficacious and safer than vitamin K antagonists. The use of these molecules (Dabigatran, Apixaban, Rivaroxaban, Betrixaban, Edoxaban) is constantly rising in daily practice. However, while available data suggest that NOAC/DOAC use is safe, dosage should be adjusted based on renal or liver function. It should be acknowledged that commonly available blood tests [Prothrombin Time (PT) and partial thromboplastin time (PTT)] are not indicated to monitor the anticoagulant activity of these compounds. With the exception of dabigatran, we currently lack of an antidote to reverse the anticoagulant effect of NOAC/DOAC. We herein review available evidence on NOAC/DOAC pharmacokinetic, risk factors for bleeding, interventions to reverse the anticoagulant activity in case of hemorrhages or need of urgent surgery and/or NOAC/DOAC overdose or side effects. PMID:27545637

  12. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation

    PubMed Central

    Douketis, James D.; Spyropoulos, Alex C.; Kaatz, Scott; Becker, Richard C.; Caprini, Joseph A.; Dunn, Andrew S.; Garcia, David A.; Jacobson, Alan; Jaffer, Amir K.; Kong, David F.; Schulman, Sam; Turpie, Alexander G.G.; Hasselblad, Vic; Ortel, Thomas L.

    2016-01-01

    BACKGROUND It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. METHODS We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. RESULTS In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], −0.6 to 0.8; P = 0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P = 0.005 for superiority). CONCLUSIONS In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to

  13. New anticoagulants for atrial fibrillation.

    PubMed

    Sobieraj-Teague, Magdalena; O'Donnell, Martin; Eikelboom, John

    2009-07-01

    Atrial fibrillation is already the most common clinically significant cardiac arrhythmia and a common cause of stroke. Vitamin K antagonists are very effective for the prevention of cardioembolic stroke but have numerous limitations that limit their uptake in eligible patients with AF and reduce their effectiveness in treated patients. Multiple new anticoagulants are under development as potential replacements for vitamin K antagonists. Most are small synthetic molecules that target factor IIa (e.g., dabigatran etexilate, AZD-0837) or factor Xa (e.g., rivaroxaban, apixaban, betrixaban, DU176b, idrabiotaparinux). These drugs have predictable pharmacokinetics that allow fixed dosing without laboratory monitoring, and are being compared with vitamin K antagonists or aspirin in phase III clinical trials [corrected]. A new vitamin K antagonist (ATI-5923) with improved pharmacological properties compared with warfarin is also being evaluated in a phase III trial. None of the new agents have as yet been approved for clinical use. PMID:19739042

  14. [Direct oral anticoagulant associated bleeding].

    PubMed

    Godier, A; Martin, A-C; Rosencher, N; Susen, S

    2016-07-01

    Direct oral anticoagulants (DOAC) are recommended for stroke prevention in atrial fibrillation and for the treatment of venous thromboembolism. However, they are associated with hemorrhagic complications. Management of DOAC-induced bleeding remains challenging. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. Therapeutic options also include antidotes: idarucizumab, antidote for dabigatran, has been approved for use whereas andexanet alpha, antidote for anti-Xa agents, and aripazine, antidote for all DOAC, are under development. Other options include hemodialysis for the treatment of dabigatran-associated bleeding and administration of oral charcoal if recent DOAC ingestion. DOAC plasma concentration measurement is necessary to guide DOAC reversal. We propose an update on DOAC-associated bleeding, integrating the availability of dabigatran antidote and the critical place of DOAC concentration measurements. PMID:27297642

  15. [Prophylaxis of thromboembolism in atrial fibrillation: new oral anticoagulants and left atrial appendage closure].

    PubMed

    Zeus, Tobias; Kelm, Malte; Bode, Christoph

    2015-08-01

    Thrombo-embolic prophylaxis is a key element within the therapy of atrial fibrillation/atrial flutter. Besides new oral anticoagulants the concept of left atrial appendage occlusion has approved to be a good alternative option, especially in patients with increased risk of bleeding. PMID:26261929

  16. Laboratory assessment of the anticoagulant effects of the next generation of oral anticoagulants.

    PubMed

    Garcia, D; Barrett, Y C; Ramacciotti, E; Weitz, J I

    2013-02-01

    In contrast to vitamin K antagonists, which reduce the functional levels of several coagulation factors, the new oral anticoagulants specifically target either thrombin or factor Xa. These new agents have such predictable pharmacokinetics and pharmacodynamics that routine coagulation monitoring is unnecessary. However, there are still some situations in which measurement of anticoagulant effect may be required. The coagulation assays that are used to monitor heparin derivatives or vitamin K antagonists may not always accurately reflect the anticoagulant activity of the new oral anticoagulants, and specialized assays may be needed. In this article, we: (i) identify situations in which assessment of anticoagulant effect may aid treatment decisions; (ii) describe the effects of the new oral anticoagulants on the various coagulation tests; (iii) review the specialized coagulation assays that have been developed to measure the anticoagulant effects of the new oral anticoagulants; and (iv) provide a clinical perspective on the role of coagulation testing in the clinical management of patients treated with the new oral anticoagulants. PMID:23216682

  17. What Are Anticoagulants and Antiplatelet Agents?

    MedlinePlus

    ... Anticoagulants and antiplatelet agents are medicines that reduce blood clotting in an artery, a vein or the heart. ... are drugs that are given to prevent your blood from clotting or prevent existing clots from getting larger. They ...

  18. Lemierre Syndrome—Should We Anticoagulate? A Case Report and Review of the Literature

    PubMed Central

    Phua, C.K.; Chadachan, V.M.; Acharya, R.

    2013-01-01

    Lemierre syndrome is an uncommon condition classically described in acute oropharyngeal infection with septic thrombophlebitis of the internal jugular vein and metastatic septic embolism particularly to the lungs. It is commonly described in young healthy adults with isolation of Fusobacterium necrophorum. We describe a case of Lemierre syndrome in a 50-year-old man with newly diagnosed diabetes mellitus presenting with a neck abscess secondary to Klebsiella pneumoniae. Our patient made good recovery to appropriate antimicrobial therapy, prompt surgical drainage, and anticoagulation. Anticoagulation remains controversial and we review the literature for its role in Lemierre syndrome. PMID:24436600

  19. New antiplatelet drugs and new oral anticoagulants.

    PubMed

    Koenig-Oberhuber, V; Filipovic, M

    2016-09-01

    In our daily anaesthetic practice, we are confronted with an increasing number of patients treated with either antiplatelet or anticoagulant agents. During the last decade, changes have occurred that make the handling of antithrombotic medication a challenging part of anaesthetic perioperative management. In this review, the authors discuss the most important antiplatelet and anticoagulant drugs, the perioperative management, the handling of bleeding complications, and the interpretation of some laboratory analyses related to these agents. PMID:27566810

  20. Potential role of new anticoagulants for prevention and treatment of venous thromboembolism in cancer patients

    PubMed Central

    Gómez-Outes, Antonio; Suárez-Gea, M Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio; Rocha, Eduardo

    2013-01-01

    Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Low molecular weight heparins are the preferred option for anticoagulation in cancer patients according to current clinical practice guidelines. Fondaparinux may also have a place in prevention of VTE in hospitalized cancer patients with additional risk factors and for initial treatment of VTE. Although low molecular weight heparins and fondaparinux are effective and safe, they require daily subcutaneous administration, which may be problematic for many patients, particularly if long-term treatment is needed. Studying anticoagulant therapy in oncology patients is challenging because this patient group has an increased risk of VTE and bleeding during anticoagulant therapy compared with the population without cancer. Risk factors for increased VTE and bleeding risk in these patients include concomitant treatments (surgery, chemotherapy, placement of central venous catheters, radiotherapy, hormonal therapy, angiogenesis inhibitors, antiplatelet drugs), supportive therapies (ie, steroids, blood transfusion, white blood cell growth factors, and erythropoiesis-stimulating agents), and tumor-related factors (local vessel damage and invasion, abnormalities in platelet function, and number). New anticoagulants in development for prophylaxis and treatment of VTE include parenteral compounds for once-daily administration (ie, semuloparin) or once-weekly dosing (ie, idraparinux and idrabiotaparinux), as well as orally active compounds (ie, dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban). In the present review, we discuss the pharmacology of the new anticoagulants, the results of clinical trials testing these new compounds in VTE, with special emphasis on studies that included cancer patients, and their potential advantages and drawbacks compared with existing therapies. PMID:23674896

  1. Diagnosis and treatment of secondary anticoagulant rodenticide toxicosis in a red-tailed hawk (Buteo jamaicensis).

    PubMed

    Murray, Maureen; Tseng, Florina

    2008-03-01

    Anticoagulant rodenticides inhibit the activation of vitamin K-ependent clotting factors, resulting in fatal hemorrhage. Nontarget species are exposed to these rodenticides primarily by direct consumption of baits or secondarily by consumption of poisoned prey. The diagnosis of anticoagulant rodenticide toxicosis is more challenging in birds than in mammals because of the limited availability of laboratory tests to evaluate avian coagulation. In addition, the presenting signs in birds may differ from those commonly seen in mammals. Treatment for acute blood loss and therapy with vitamin K1 can result in a favorable outcome in birds. This report describes the presenting signs, diagnosis, and successful treatment of a red-tailed hawk (Buteo jamaicensis) with secondary anticoagulant rodenticide toxicosis. PMID:18543601

  2. A case of warfarin skin necrosis despite enoxaparin anticoagulation in a patient with protein S deficiency.

    PubMed

    Tai, Chau Y; Ierardi, Ralph; Alexander, James B

    2004-03-01

    Warfarin-induced skin necrosis is a rare complication associated with the use of oral anticoagulants. Most patients develop this at the initiation of therapy, often while still receiving intravenous unfractionated heparin (UFH). Recently, low-molecular-weight heparins (LMWHs) have gained wider use, providing an option for outpatient treatment of deep-vein thrombosis. The treatment protocols are similar to UFH, including the early initiation of oral anticoagulation with warfarin. A Medline search failed to reveal any cases of warfarin-induced skin necrosis while using a LMWH. We present a patient with protein S deficiency who developed warfarin skin necrosis despite appropriate anticoagulation with enoxaparin, and review the chemical and clinical difference between UFH and LMWH. PMID:15253263

  3. Evolving Treatments for Arterial and Venous Thrombosis: Role of the Direct Oral Anticoagulants.

    PubMed

    Chan, Noel C; Eikelboom, John W; Weitz, Jeffrey I

    2016-04-29

    The direct oral anticoagulants (DOACs) represent a major advance in oral anticoagulant therapy and have replaced the vitamin K antagonists as the preferred treatment for many indications. By simplifying long-term anticoagulant therapy and improving its safety, the DOACs have the potential to reduce the global burden of thrombosis. Postmarketing studies suggest that the favorable results achieved with DOACs in the randomized controlled trials can be readily translated into practice, but highlight the need for appropriate patient, drug and dose selection, and careful follow-up. Leveraging on their success to date, ongoing studies are assessing the utility of DOACs for the prevention of thrombosis in patients with embolic stroke of unknown source, heart failure, coronary artery disease, peripheral artery disease, antiphospholipid syndrome, and cancer. The purpose of this article is to (1) review the pharmacology of the DOACs, (2) describe the advantages of the DOACs over vitamin K antagonists, (3) summarize the experience with the DOACs in established indications, (4) highlight current challenges and limitations, (5) highlight potential new indications; and (6) identify future directions for anticoagulant therapy. PMID:27126650

  4. Is long-term anticoagulation after acute thromboembolic limb ischemia always necessary?

    PubMed Central

    Forbes, Thomas L.; DeRose, Guy; Harris, Kenneth A.

    2002-01-01

    Objective After thromboembolectomy, patients with acute limb ischemia often receive anticoagulant therapy to prevent recurrent events. Patients with atrial fibrillation or cardiac thrombus have a higher risk of recurrent emboli than those without these risk factors. This study examines the importance of long-term anticoagulation in these 2 groups. Design A review of patients presenting with acute limb ischemia over a 5-year period (1994–1999). Setting A university-affiliated medical centre. Patients Fifty patients divided into 2 groups: 19 (38%) patients with atrial fibrillation (group 1) and 31 (62%) patients with no atrial fibrillation or cardiac thrombus (group 2) as confirmed by transthoracic echocardiography. Intervention All patients underwent surgical thromboembolectomy and received postoperative anticoagulant therapy. Outcome measures Mortality, limb loss, further thromboembolic events and bleeding complications as determined by telephone survey. Results There was a significant difference in 5-year survival (group 1, 84%; group 2, 64%) and early limb loss (group 1, 0%; group 2, 13%). Further thromboembolic events and bleeding complications were rare but were more common in group 1. In group 2 there were no instances of recurrent thromboemboli and no bleeding complications although only 39% of patients in this group were taking angicoagulants at the end of the study period. Conclusions Patients with extremity thromboemboli without atrial fibrillation or cardiac thrombus may not be at the same risk for recurrent events as those with these risk factors, and long-term anticoagulant therapy may not be as necessary in this group. PMID:12387535

  5. Polysulfated Trehalose as a Novel Anticoagulant Agent with Dual Mode of Action

    PubMed Central

    Rashid, Qudsia; Abid, Mohammad; Gupta, Neha; Tyagi, Tarun; Ashraf, Mohammad Z.; Jairajpuri, Mohamad Aman

    2015-01-01

    Physiological hemostatic balance is a coordinated outcome of counteracting coagulation and fibrinolytic systems. An imbalance of procoagulant and anticoagulant factors may result in life threatening thromboembolism. Presently, anticoagulant administration is the first line of therapy for the treatment of these conditions and several anticoagulants have been approved, including various forms of heparin. However, the polyanionic nature and multispecificity of heparin pose several complications. Generally, the polysulfated compounds with antithrombotic potential are thought to have feasible synthetic procedures with much less bleeding, thus having favourable safety profiles. Here we report the synthesis of a novel compound, trehalose octasulfate and the assessment of its anticoagulation potential. Molecular docking of trehalose and trehalose octasulfate with antithrombin showed a specificity switch in binding affinity on sulfation, where trehalose octasulfate interacts with critical residues of AT that are either directly involved in heparin binding or in the conformational rearrangement of AT on heparin binding. An in vitro analysis of trehalose octasulfate demonstrated prolonged clotting time. Lead compound when intravenously injected in occlusion induced thrombotic rats showed remarkable reduction in the size and weight of the clot at a low dose. Delay in coagulation time was observed by analysing blood plasma isolated from rats preinjected with trehalose octasulfate. A decrease in Adenosine 5′-Diphosphate (ADP) induced platelet aggregation indicated a probable dual anticoagulant and antiplatelet mechanism of action. To summarize, this study presents trehalose octasulfate as a novel, effective, dual acting antithrombotic agent. PMID:25866798

  6. Anticoagulation, ferrotoxicity and the future of translational lung cancer research

    PubMed Central

    2016-01-01

    Numerous studies have shown that elements of coagulation reactions mediate tumor cell proliferation, motility (invasiveness), tissue remodeling and metastasis. Coagulation activation is virtually a universal feature of human malignancy that differs from the clotting response to injury in that it is self-perpetuating rather than self-attenuating. Coagulation activation participates in tumor matrix deposition and local inflammation, and predicts subsequent cancer risk and adverse cancer outcomes. Several clinical trials of anticoagulants have shown improved outcomes in small cell carcinoma of the lung (SCCL) that have been correlated with assembly on the tumor cells of an intact coagulation pathway. However, variable efficacy of anticoagulant therapy has raised doubts about the coagulation hypothesis. Recently, initiators of coagulation and fibrinolytic pathways have been identified that mediate tumor inception and progression. Notable among these is oxidative stress driven by iron-catalyzed reactive oxygen species that may be the basis for local coagulation activation, tumor matrix deposition, inflammation and aberrant properties characteristic of the malignant phenotype. Recognition of important biological characteristics of individual tumor types, disease stage, choice of standard therapy including chemotherapy and the iron status of the host may clarify mechanisms. All of these are subject to modification based on controlled clinical trial design. Further tests of the coagulation hypothesis may lead to novel, low cost and relatively non-toxic approaches to treatment of malignancy including lung cancer that contrast with certain current cancer treatment paradigms. PMID:27413710

  7. Anticoagulation, ferrotoxicity and the future of translational lung cancer research.

    PubMed

    Zacharski, Leo R

    2016-06-01

    Numerous studies have shown that elements of coagulation reactions mediate tumor cell proliferation, motility (invasiveness), tissue remodeling and metastasis. Coagulation activation is virtually a universal feature of human malignancy that differs from the clotting response to injury in that it is self-perpetuating rather than self-attenuating. Coagulation activation participates in tumor matrix deposition and local inflammation, and predicts subsequent cancer risk and adverse cancer outcomes. Several clinical trials of anticoagulants have shown improved outcomes in small cell carcinoma of the lung (SCCL) that have been correlated with assembly on the tumor cells of an intact coagulation pathway. However, variable efficacy of anticoagulant therapy has raised doubts about the coagulation hypothesis. Recently, initiators of coagulation and fibrinolytic pathways have been identified that mediate tumor inception and progression. Notable among these is oxidative stress driven by iron-catalyzed reactive oxygen species that may be the basis for local coagulation activation, tumor matrix deposition, inflammation and aberrant properties characteristic of the malignant phenotype. Recognition of important biological characteristics of individual tumor types, disease stage, choice of standard therapy including chemotherapy and the iron status of the host may clarify mechanisms. All of these are subject to modification based on controlled clinical trial design. Further tests of the coagulation hypothesis may lead to novel, low cost and relatively non-toxic approaches to treatment of malignancy including lung cancer that contrast with certain current cancer treatment paradigms. PMID:27413710

  8. New issues in oral anticoagulants.

    PubMed

    Francis, Charles W

    2008-01-01

    Polymorphisms in CYP2C9, a critical cytochrome P-450 enzyme in the metabolism of warfarin, alters its clearance and affects dosing. CYP*1 has higher activity than either the *2 or *3 variants, and patients with the *2 or *3 variants require a lower dose. VKORC1 is the enzyme inhibited by warfarin, and its levels are affected by several polymorphisms that can be divided into high or low level haplotypes, and patients with high level haplotypes require higher warfarin doses. The use of algorithms for dosing that incorporate pharmacogenomic information perform better than those using clinical data alone. Considerable effort is ongoing to develop new oral anticoagulants as alternatives to warfarin, and three agents are in advanced development. Dabigatran is an oral direct thrombin inhibitor that has been compared with enoxaparin for prevention of VTE following hip or knee replacement. Based on non-inferiority results in European trials, it has now been approved for marketing in Europe. Phase III trials with a new oral Xa inhibitor, rivaroxaban, have been completed in hip or knee replacement, and rivaroxaban was superior to enoxaparin in prevention of VTE with no increase in bleeding complications. Phase III studies with apixaban, another oral Xa inhibitor, are in progress. These agents are also being evaluated in large studies for prevention of stroke in atrial fibrillation and for VTE treatment. PMID:19074093

  9. Cystamine preparations exhibit anticoagulant activity.

    PubMed

    Aleman, Maria M; Holle, Lori A; Stember, Katherine G; Devette, Christa I; Monroe, Dougald M; Wolberg, Alisa S

    2015-01-01

    Transglutaminases are a superfamily of isoenzymes found in cells and plasma. These enzymes catalyze the formation of ε-N-(γ-glutamyl)-lysyl crosslinks between proteins. Cystamine blocks transglutaminase activity and is used in vitro in human samples and in vivo in mice and rats in studies of coagulation, immune dysfunction, and inflammatory disease. These studies have suggested cystamine blocks fibrin crosslinking and has anti-inflammatory effects, implicating transglutaminase activity in the pathogenesis of several diseases. We measured the effects of cystamine on fibrin crosslinking, tissue factor-triggered plasma clot formation and thrombin generation, and coagulation factor enzymatic activity. At concentrations that blocked fibrin crosslinking, cystamine also inhibited plasma clot formation and reduced thrombin generation. Cystamine inhibited the amidolytic activity of coagulation factor XI and thrombin towards chromogenic substrates. These findings demonstrate that cystamine exhibits anticoagulant activity during coagulation. Given the close relationship between coagulation and inflammation, these findings suggest prior studies that used cystamine to implicate transglutaminase activity in disease pathogenesis warrant re-examination. PMID:25915545

  10. Cystamine Preparations Exhibit Anticoagulant Activity

    PubMed Central

    Aleman, Maria M.; Holle, Lori A.; Stember, Katherine G.; Devette, Christa I.; Monroe, Dougald M.; Wolberg, Alisa S.

    2015-01-01

    Transglutaminases are a superfamily of isoenzymes found in cells and plasma. These enzymes catalyze the formation of ε-N-(γ-glutamyl)-lysyl crosslinks between proteins. Cystamine blocks transglutaminase activity and is used in vitro in human samples and in vivo in mice and rats in studies of coagulation, immune dysfunction, and inflammatory disease. These studies have suggested cystamine blocks fibrin crosslinking and has anti-inflammatory effects, implicating transglutaminase activity in the pathogenesis of several diseases. We measured the effects of cystamine on fibrin crosslinking, tissue factor-triggered plasma clot formation and thrombin generation, and coagulation factor enzymatic activity. At concentrations that blocked fibrin crosslinking, cystamine also inhibited plasma clot formation and reduced thrombin generation. Cystamine inhibited the amidolytic activity of coagulation factor XI and thrombin towards chromogenic substrates. These findings demonstrate that cystamine exhibits anticoagulant activity during coagulation. Given the close relationship between coagulation and inflammation, these findings suggest prior studies that used cystamine to implicate transglutaminase activity in disease pathogenesis warrant re-examination. PMID:25915545

  11. Efficacy of long-term anticoagulant treatment in subgroups of patients after myocardial infarction.

    PubMed Central

    van Bergen, P. F.; Deckers, J. W.; Jonker, J. J.; van Domburg, R. T.; Azar, A. J.; Hofman, A.

    1995-01-01

    OBJECTIVE--To investigate the efficacy of long term oral anticoagulant treatment in subgroups of patients after myocardial infarction. DESIGN--Analysis of the effect of anticoagulant treatment in subgroups of hospital survivors of myocardial infarction based upon age, gender, history of hypertension, previous myocardial infarction, smoking habits, diabetes mellitus, Killip class, anterior location of infarction, thrombolytic therapy, and use of beta blockers. SUBJECTS--Participants of a multicentre, randomised, double blind, placebo controlled trial that assessed the effect of oral anticoagulant treatment on mortality as well as cerebrovascular and cardiovascular morbidity in 3404 hospital survivors of acute myocardial infarction. MAIN OUTCOME MEASURES--The effect of anticoagulant treatment on recurrent myocardial infarction, cerebrovascular events, and vascular events (the composite endpoint of reinfarction, cerebrovascular event, and vascular death). RESULTS--Long term anticoagulant treatment was associated with a reduction in mortality of 10% (95% confidence interval -11% to 27%), recurrent myocardial infarction of 53% (41% to 62%), cerebrovascular events of 40% (10% to 60%) and vascular events of 35% (24% to 45%). Treatment effect with respect to recurrent myocardial infarction was comparable among all subgroups of patients. Although treatment effect appeared to be somewhat smaller in females than in males (-11% v -45%), and in patients with diabetes compared to those without (-14% v -42%) with respect to vascular events, none of these differences reached statistical significance. In multivariate analysis, more advanced age, previous myocardial infarction, diabetes mellitus, and heart failure during admission were independently associated with increased incidence of cardiovascular complications. CONCLUSIONS--The relative benefit of long term anticoagulant therapy in survivors of myocardial infarction is not modified by known prognostic factors for

  12. Periprocedural anticoagulation of patients undergoing pericardiocentesis for cardiac tamponade complicating catheter ablation of atrial fibrillation.

    PubMed

    Lin, Tao; Bai, Rong; Chen, Ying-wei; Yu, Rong-hui; Tang, Ri-bo; Sang, Cai-hua; Li, Song-nan; Ma, Chang-sheng; Dong, Jian-zeng

    2015-01-01

    Anticoagulation of patients with cardiac tamponade (CT) complicating catheter ablation of atrial fibrillation (AF) is an ongoing problem. The aim of this study was to survey the clinical practice of periprocedural anticoagulation in such patients. This study analyzed the periprocedural anticoagulation of 17 patients with CT complicating AF ablation. Emergent pericardiocentesis was performed once CT was confirmed. The mean drained volume was 410.0 ± 194.1 mL. Protamine sulfate was administered to neutralize heparin (1 mg neutralizes 100 units heparin) in 11 patients with persistent pericardial bleeding and vitamin K1 (10 mg) was given to reverse warfarin in 3 patients with supratherapeutic INR (INR > 2.1). Drainage catheters were removed 12 hours after echocardiography confirmed absence of intrapericardial bleeding and anticoagulation therapy was restored 12 hours after removing the catheter. Fifteen patients took oral warfarin and 10 of them were given subcutaneous injection of LMWH (1 mg/kg, twice daily) as a bridge to resumption of systemic anticoagulation with warfarin. Two patients with a small amount of persistent pericardial effusion were given LMWH on days 5 and 13, and warfarin on days 6 and 24. The dosage of warfarin was adjusted to keep the INR within 2-3 in all patients. After 12 months of follow-up, all patients had no neurological events and no occurrence of delayed CT. The results showed that it was effective and safe to resume anticoagulation therapy 12 hours after removal of the drainage catheter. This may help to prevent thromboembolic events following catheter ablation of AF. PMID:25503659

  13. Effective management of venous thromboembolism in the community: non-vitamin K antagonist oral anticoagulants

    PubMed Central

    Patel, Raj

    2016-01-01

    Anticoagulation therapy is essential for the effective treatment and secondary prevention of venous thromboembolism (VTE). For many years, anticoagulation for acute VTE was limited to the use of initial parenteral heparin, overlapping with and followed by a vitamin K antagonist. Although highly effective, this regimen has several limitations and is particularly challenging when given in an ambulatory setting. Current treatment pathways for most patients with deep-vein thrombosis typically involve initial hospital or community-based ambulatory care with subsequent follow-up in a secondary care setting. With the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) into routine clinical practice, it is now possible for the initial acute management of patients with deep-vein thrombosis to be undertaken by primary care. As hospital admissions associated with VTE become shorter, primary care will play an increasingly important role in the long-term management of these patients. Although the NOACs can potentially simplify patient management and improve clinical outcomes, primary care physicians may be less familiar with these new treatments compared with traditional therapy. To assist primary care physicians in further understanding the role of the NOACs, this article outlines the main differences between NOACs and traditional anticoagulation therapy and discusses the benefit–risk profile of the different NOACs in the treatment and secondary prevention of recurrent VTE. Key considerations for the use of NOACs in the primary care setting are highlighted, including dose transition, risk assessment and follow-up, duration of anticoagulant therapy, how to minimize bleeding risks, and the importance of patient education and counseling. PMID:27217793

  14. Changing practice of anticoagulation: will target-specific anticoagulants replace warfarin?

    PubMed

    Arepally, Gowthami M; Ortel, Thomas L

    2015-01-01

    The target-specific oral anticoagulants are a class of agents that inhibit factor Xa or thrombin. They are effective and safe compared to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation and for the treatment of venous thromboembolism, and they are comparable to low-molecular-weight heparin for thromboprophylaxis after hip or knee arthroplasty. For other indications, however, such as the prevention of stroke in patients with mechanical heart valves, initial studies have been unfavorable for the newer agents, leaving warfarin the anticoagulant of choice. Further studies are needed before the target-specific anticoagulants can be recommended for patients with cancer-associated thrombosis or heparin-induced thrombocytopenia. Concerns also persist about difficulties with the laboratory assessment of anticoagulant effect and the lack of a specific reversal agent. For these reasons, we anticipate that the vitamin K antagonists will continue to be important anticoagulants for years to come. PMID:25587651

  15. Race against the clock: overcoming challenges in the management of anticoagulant-associated intracerebral hemorrhage.

    PubMed

    Le Roux, Peter; Pollack, Charles V; Milan, Melissa; Schaefer, Alisa

    2014-08-01

    Patients receiving anticoagulation therapy who present with any type of intracranial hemorrhage--including subdural hematoma, epidural hematoma, subarachnoid hemorrhage, and intracerebral hemorrhage (ICH)--require urgent correction of their coagulopathy to prevent hemorrhage expansion, limit tissue damage, and facilitate surgical intervention as necessary. The focus of this review is acute ICH, but the principles of management for anticoagulation-associated ICH (AAICH) apply to patients with all types of intracranial hemorrhage, whether acute or chronic. A number of therapies--including fresh frozen plasma (FFP), intravenous vitamin K, activated and inactivated prothrombin complex concentrates (PCCs), and recombinant activated factor VII (rFVIIa)--have been used alone or in combination to treat AAICH to reverse anticoagulation, help achieve hemodynamic stability, limit hematoma expansion, and prepare the patient for possible surgical intervention. However, there is a paucity of high-quality data to direct such therapy. The use of 3-factor PCC (activated and inactivated) and rFVIIa to treat AAICH constitutes off-label use of these therapies in the United States. However, in April 2013, the US Food and Drug Administration (FDA) approved Kcentra (a 4-factor PCC) for the urgent reversal of vitamin K antagonist (VKA) anticoagulation in adults with acute major bleeding. Plasma is the only other product approved for this use in the United States. (1) Inconsistent recommendations, significant barriers (e.g., clinician-, therapy-, or logistics-based barriers), and a lack of approved treatment pathways in some institutions can be potential impediments to timely and evidence-based management of AAICH with available therapies. Patient assessment, therapy selection, whether to use a reversal or factor repletion agent alone or in combination with other agents, determination of site-of-care management, eligibility for neurosurgery, and potential hematoma evacuation are the

  16. Use and Outcomes Associated With Bridging During Anticoagulation Interruptions in Patients With Atrial Fibrillation

    PubMed Central

    Peterson, Eric D.; Kim, Sunghee; Thomas, Laine; Gersh, Bernard J.; Fonarow, Gregg C.; Kowey, Peter R.; Mahaffey, Kenneth W.; Sherwood, Matthew W.; Chang, Paul; Piccini, Jonathan P.; Ansell, Jack

    2015-01-01

    Background— Temporary interruption of oral anticoagulation for procedures is often required, and some propose using bridging anticoagulation. However, the use and outcomes of bridging during oral anticoagulation interruptions in clinical practice are unknown. Methods and Results— The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry is a prospective, observational registry study of US outpatients with atrial fibrillation. We recorded incident temporary interruptions of oral anticoagulation for a procedure, including the use and type of bridging therapy. Outcomes included multivariable-adjusted rates of myocardial infarction, stroke or systemic embolism, major bleeding, cause-specific hospitalization, and death within 30 days. Of 7372 patients treated with oral anticoagulation, 2803 overall interruption events occurred in 2200 patients (30%) at a median follow-up of 2 years. Bridging anticoagulants were used in 24% (n=665), predominantly low-molecular-weight heparin (73%, n=487) and unfractionated heparin (15%, n=97). Bridged patients were more likely to have had prior cerebrovascular events (22% versus 15%; P=0.0003) and mechanical valve replacements (9.6% versus 2.4%; P<0.0001); however, there was no difference in CHA2DS2-VASc scores (scores ≥2 in 94% versus 95%; P=0.5). Bleeding events were more common in bridged than nonbridged patients (5.0% versus 1.3%; adjusted odds ratio, 3.84; P<0.0001). The incidence of myocardial infarction, stroke or systemic embolism, major bleeding, hospitalization, or death within 30 days was also significantly higher in patients receiving bridging (13% versus 6.3%; adjusted odds ratio, 1.94; P=0.0001). Conclusions— Bridging anticoagulation is used in one quarter of anticoagulation interruptions and is associated with higher risk for bleeding and adverse events. These data do not support the use of routine bridging, and additional data are needed to identify best practices concerning

  17. Lupus-anticoagulant testing at NOAC trough levels.

    PubMed

    Ratzinger, Franz; Lang, Mona; Belik, Sabine; Jilma-Stohlawetz, Petra; Schmetterer, Klaus G; Haslacher, Helmuth; Perkmann, Thomas; Quehenberger, Peter

    2016-08-01

    Non-vitamin K antagonist oral anticoagulants (NOAC), including rivaroxaban, apixaban or dabigatran, regularly show relevant effects on coagulation tests, making the interpretation of results difficult. The aim of this study was to evaluate possible interferences of NOACs in trough level concentrations in lupus anticoagulant (LA) testing. Citrate plasma specimens of 30 healthy volunteers were spiked with rivaroxaban, apixaban or dabigatran in four plasma concentration levels at or below trough NOAC levels. The NOAC concentration was measured using dedicated surrogate concentration tests and a stepwise diagnostic procedure for LA-testing was applied using screening, mixing and confirmatory testing. Results were compared to NOAC-free specimens. Starting with a plasma concentration of 12.5 ng/ml, dabigatran-spiked specimens showed significant prolongations in the lupus anticoagulant-sensitive activated partial thromboplastin time (aPTT-LA) as well as in the Dilute Russell viper venom time (dRVVT), leading to 43.3 % false positives in confirmatory testing in the dRVVT. In contrast, rivaroxaban, beginning with 7.5 ng/ml, exclusively affected dRVVT-based tests. In confirmatory tests, 30.0 % of rivaroxaban-spiked specimens showed false positive results. Starting with 18.75 ng/ml apixaban, a significant prolongation of the dRVVT and up to 20.7 % false positives in confirmatory tests were found. In contrast to other NOACs tested, apixaban did not present with a dose-dependent increase of the dRVVT ratio. In conclusion, the rate of false positive results in LA-testing is unacceptably high at expected trough levels of NOACs. Even at plasma concentrations below the LLOQ of commercially available surrogate tests, LA testing is best avoided in patients with NOAC therapy. PMID:27075441

  18. The new oral anticoagulants: a challenge for hospital formularies.

    PubMed

    Merli, Geno J

    2012-08-01

    Introduction Over the past 60 years, clinicians have used vitamin K antagonists, primarily warfarin, as the sole oral anticoagulants for managing a variety of thrombotic disorders. Warfarin, which requires frequent monitoring, has a variable dose response, a narrow therapeutic index, and numerous drug and dietary interactions. However, intravenous and subcutaneous agents, such as unfractionated heparin, low-molecular-weight heparin, direct thrombin inhibitors, and pentasaccharide, have been introduced over the past 30 years for managing thromboembolic disorders. Recently, 5 new oral anticoagulants, dabigatran, rivaroxaban, apixaban, endoxaban, and betrixaban, have been introduced into clinical trials. Apixaban, rivaroxaban, endoxaban, and betrixaban are specific direct inhibitors of factor Xa, while dabigatran inhibits factor IIa. These drugs have a pharmacological profile that does not require monitoring in order to adjust therapy, which is the mainstay of warfarin management. In addition, these new medications have not shown any major issues regarding food interactions; rather, they demonstrate the potential for limited drug-drug interactions due to their limited metabolism through the cytochrome P450 system. This unique pharmacokinetic profile may provide clinicians with a new era of managing thromboembolic disorders. Two of these agents, dabigatran and rivaroxaban, have been approved by the US Food and Drug Administration (FDA) for stroke prevention in patients with nonvalvular atrial fibrillation (AF); in addition, rivaroxaban can be used in the prevention of venous thromboembolism (VTE) in total hip and knee arthroplasty during the acute and extended periods of risk. However, the challenge for hospital formularies will be the appropriate use and management of these new medications as they become integrated into outpatient care. In order to better understand the issues that pharmacy and therapeutics committees will encounter, a review of the 2 FDA

  19. Atrial Fibrillation Ablation without Interruption of Anticoagulation.

    PubMed

    Santangeli, Pasquale; Di Biase, Luigi; Sanchez, Javier E; Horton, Rodney; Natale, Andrea

    2011-01-01

    Atrial fibrillation (AF) can be cured by pulmonary vein antrum isolation (PVAI) in a substantial proportion of patients. The high efficacy of PVAI is partially undermined by a small but concrete periprocedural risk of complications, such as thromboembolic events and bleeding. A correct management of anticoagulation is essential to prevent such complications. Performing PVAI without interruption of oral anticoagulation has been demonstrated feasible by our group in previous studies. Recently, we reported that continuation of therapeutic warfarin during radiofrequency catheter ablation consistently reduces the risk of periprocedural stroke/transient ischemic attack without increasing the risk of hemorrhagic events. Of note, interrupting warfarin anticoagulation may actually increase the risk of stroke even when bridged with heparin. The latter strategy is also associated with an increased risk of minor bleeding. With regard to major bleeding, we found no significant difference between patients with a therapeutic INR and those who were bridged with heparin. Therefore, continuation of therapeutic warfarin during ablation of AF appears to be the best anticoagulation strategy. In this paper we summarize our experience with AF ablation without interruption of anticoagulation. PMID:21577267

  20. Current practice of antiplatelet and anticoagulation management in post-cardiac surgery patients: a national audit.

    PubMed

    Hosmane, Sharath; Birla, Rashmi; Marchbank, Adrian

    2012-04-01

    The Audit and Guidelines Committee of the European Association for Cardio-Thoracic Surgery recently published a guideline on antiplatelet and anticoagulation management in cardiac surgery. We aimed to assess the awareness of the current guideline and adherence to it in the National Health Service through this National Audit. We designed a questionnaire consisting of nine questions covering various aspects of antiplatelet and anticoagulation management in post-cardiac surgery patients. A telephonic survey of the on-call cardiothoracic registrars in all the cardiothoracic centres across the UK was performed. All 37 National Health Service hospitals in the UK with 242 consultants providing adult cardiac surgical service were contacted. Twenty (54%) hospitals had a unit protocol for antiplatelet and anticoagulation management in post-cardiac surgery. Only 23 (62.2%) registrars were aware of current European Association for Cardio-Thoracic Surgery guidelines. Antiplatelet therapy is variable in the cardiac surgical units across the country. Low-dose aspirin is commonly used despite the recommendation of 150-300 mg. The loading dose of aspirin within 24 h as recommended by the guideline is followed only by 60.7% of surgeons. There was not much deviation from the guideline with respect to the anticoagulation therapy. PMID:22235003

  1. [Treatment standards of the oral anticoagulant in patients with idiopathic pulmonary embolism].

    PubMed

    Kowalski, Zbigniew; Kowalski, Piotr; Grzegorek, Damian

    2016-07-01

    The optimal and the most effective treatment of pulmonary embolism is still a matter of concern and each day sees a new set of challenges for the world of medicine. The progress, has been made in recent years, improved quality of life and caused much better treatment results. This is difficult issue in patients, receiving anticoagulant therapy, because they require an individual approach and adjustability to the therapeutic possibilities. The benefits of long-term anticoagulant therapy, which decreases relapses of idiopathic venous thromboembolism and diminishes risk of thromboembolic complications, should be taking under consideration. It is still a matter of dispute the time of carrying out of treatment, especially after the first life idiopathic episode of pulmonary embolism. The purpose of this paper is an overview and a summary of the foregoing achievements concerned the standards of idiopathic pulmonary embolism treatment, expecting benefits flowing with using new oral anticoagulants, as an alternative to known for decades Vitamin K antagonist drugs. A lot of information about new oral anticoagulants speaks in favor of their use, but unknown safety of the drugs caused searching the best strategy of pulmonary embolism treatment all the time. PMID:27590653

  2. [Treatment standards of the oral anticoagulant in patients with idiopathic pulmonary embolism].

    PubMed

    Kowalski, Zbigniew; Kowalski, Piotr; Grzegorek, Damian

    2016-08-01

    The optimal and the most effective treatment of pulmonary embolism is still a matter of concern and each day sees a new set of challenges for the world of medicine. The progress, has been made in recent years, improved quality of life and caused much better treatment results. This is difficult issue in patients, receiving anticoagulant therapy, because they require an individual approach and adjustability to the therapeutic possibilities. The benefits of long-term anticoagulant therapy, which decreases relapses of idiopathic venous thromboembolism and diminishes risk of thromboembolic complications, should be taking under consideration. It is still a matter of dispute the time of carrying out of treatment, especially after the first life idiopathic episode of pulmonary embolism. The purpose of this paper is an overview and a summary of the foregoing achievements concerned the standards of idiopathic pulmonary embolism treatment, expecting benefits flowing with using new oral anticoagulants, as an alternative to known for decades Vitamin K antagonist drugs. A lot of information about new oral anticoagulants speaks in favor of their use, but unknown safety of the drugs caused searching the best strategy of pulmonary embolism treatment all the time. PMID:27591448

  3. Stroke prevention in atrial fibrillation: established oral anticoagulants versus novel anticoagulants-translating clinical trial data into practice.

    PubMed

    Ezekowitz, Michael D; Spahr, Judy; Ghosh, Pradeepto; Corelli, Kathryn

    2014-09-01

    Anticoagulation for stroke prevention in atrial fibrillation (AF) is effective. Pivotal trials RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE-AF TIMI 48 tested novel agents against warfarin (W). In RE-LY, an open-label trial, dabigatran 150 mg BID (D150) was superior (35%) and 110 mg BID (D110) was noninferior to W. D150 reduced ischemic strokes by 25% and intracerebral bleeds by 74%, but increased major GI bleeds by 0.5 % per year. In ROCKET AF, a double-blind study, rivaroxaban 20 mg daily, downtitrated to 15 mg daily (if CrCl was <49) was noninferior for efficacy and safety, with an increase in GI bleeds. In ARISTOTLE, a double-blind study, apixaban 5 mg BID (downtitrated to 2.5 mg BID if two of the following were present: age, >80; weight, <60 kg; or serum creatinine, >1.5 mg) was superior for safety (31%), efficacy (21%), and all-cause mortality (11%). In ENGAGE-AF TIMI 48, edoxaban 60 mg once daily (30 mg once daily if CrCl 30-50 ml/min, weight <60 kg, or concomitant verapamil or quinidine) was noninferior to W for efficacy, but reduced major bleeding (20%). To translate clinical trials to practice, understanding the disease and each anticoagulant is essential. For all novel agents, rapid anticoagulation, absence of monitoring, and a short half-life differentiate them from W. Bleed rates were either noninferior or lower than for W, without an antidote. Patient compliance is critical. Knowledge of renal function is essential and maintaining patients on therapy is key. PMID:24880227

  4. Antithrombotic therapies in patients with prosthetic heart valves: guidelines translated for the clinician

    PubMed Central

    Leiria, Tiago L. L.; Lopes, Renato D.; Williams, Judson B.; Katz, Jason N.; Kalil, Renato A. K.

    2013-01-01

    Patients with prosthetic heart valves require chronic oral anticoagulation. In this clinical scenario, physicians must be mindful of the thromboembolic and bleeding risks related to chronic anticoagulant therapy. Currently, only vitamin K antagonists are approved for this indication. This paper reviews the main heart valve guidelines focusing on the use of oral anticoagulation in these patients. PMID:21327503

  5. [New oral anticoagulants in perioperative medicine].

    PubMed

    Giebl, A; Gürtler, K

    2014-04-01

    New oral anticoagulants (NOAC) inhibit factor Xa (Stuart-Prower factor) or factor IIa (thrombin) and are alternatives to vitamin K antagonists. Perioperative indications are deep vein thrombosis prophylaxis for prosthetic hip and knee replacement, therapeutic anticoagulation for deep vein thrombosis as well as the prophylaxis of stroke for patients with atrial fibrillation. Patients on NOACs pose multiple perioperative challenges for all medical disciplines involved. For non-emergency surgery, patients should be evaluated by an anesthesiolgist as early as possible to assess an optimal appointment for surgery and bridging strategy. Management of emergency procedures for patients on NOACs requires an interdisciplinary approach. The individual risk for uncontrolled bleeding versus the urgency for surgery needs to be evaluated on an individual basis. The determination of drug serum levels enables a rough estimation of anticoagulant activity. Emergency procedures in coagulopathy due to active bleeding are treated with the unspecific administration of blood products and coagulation factor concentrates. PMID:24696299

  6. Assessing patients’ anticoagulation preferences for the treatment of cancer-associated thrombosis using conjoint methodology

    PubMed Central

    Noble, Simon; Matzdorff, Axel; Maraveyas, Anthony; Holm, Majbrit V.; Pisa, Giovanni

    2015-01-01

    Low molecular weight heparins have demonstrated superiority over coumarins in the extended treatment of cancer-associated thrombosis and are recommended as first-line therapy in clinical guidelines. Non-vitamin K oral antagonists are yet to be evaluated against low molecular weight heparin for this indication. Nevertheless, a perception that patients favor oral anticoagulants over injections may lead to an increased prescribing of warfarin or non-vitamin K oral antagonists despite the evidence gap. There has been no evaluation of cancer patient preferences for anticoagulants and whether such an evidence gap is an acceptable trade-off for patients prescribed orals. We conducted a study to assess what features are most important to CAT patients regarding their choice of anticoagulant. Two modules were applied: Initial in-depth interviews with 9 patients diagnosed with cancer-associated thrombosis, and thereafter quantitative research, where a further 100 patients completed a choice-based-conjoint exercise, where 15 different scenarios were presented to identify the most important attributes of an anticoagulant. Seventy percent of the patients were treated with injected medication (low molecular weight heparin) and 30% with oral medications. Patients most valued an anticoagulant with minimal interference with their cancer treatment (39%), low thrombosis recurrence rate (24%), and low risk of major bleed (19%). Preference for oral administration over injection had moderate importance (13%). The results show that patients prefer an anticoagulant that does not interfere with their cancer treatment, suggesting the primacy of the cancer disease over venous thromboembolism in these patients. Patients also favor efficacy and safety over convenience of route of administration. PMID:26294737

  7. Possible unaware intoxication by anticoagulant rodenticide

    PubMed Central

    Dashti-Khavidaki, Simin; Ghaffari, Saba; Nassiri-Toossi, Mohsen; Amini, Mohsen; Edalatifard, Maryam

    2014-01-01

    Superwarfarin toxicity may be a serious problem. It needs high clinical suspicious in patients with bleeding diathesis without hematologic or liver diseases even in patients with apparent negative history of warfarin or other anticoagulant accessibility. Here we reported a patient with a negative history of any medical diseases or drug administration who was referred with generalized ecchymosis. Increased international normalized ratio and decreased vitamin K-dependent coagulation factors were detected in this patient. His hematologic and liver evaluations were normal. Clinical pharmacist emphasis in taking history revealed using anticoagulant rodenticide all over the farm the patient lived in that might result in unaware intoxication in this patient who suffered dementia. PMID:25535623

  8. [Pharmacologic heterogeneity of new anticoagulants].

    PubMed

    Samamaa, M-M; Conard, J; Flaujac, C; Combe, S; Horellou, M-H

    2011-12-01

    Amongst numerous promising anticoagulant molecules, rivaroxaban (Xarelto(®)), dabigatran (Pradaxa(®)) and apixaban (Eliquis(®)) have been registered outside the USA in the prevention of thromboembolic events in patients undergoing total hip or knee prosthetic replacement. Rivaroxaban however has been granted authorisation by the FDA for the thromboprophylaxis after surgery for total hip or knee surgery. Dabigatran has been granted authorisation by the FDA in non-valvular atrial fibrillation (RE-LY trial) while rivaroxaban is expecting approval in this same indication (ROCKET trial). Phase III results in the treatment and in the secondary prevention of established venous thrombosis and pulmonary embolism are encouraging. These small molecules are obtained by chemical synthesis, their molecular weight is lower than 500 daltons. Many coagulation tests may be affected by these molecules. Those modifications should be known in order to avoid misinterpretation of the tests but could also be used to measure plasma concentrations of these products. The choice of a non specific global and readily available test has been documented (Quick time for rivaroxaban and aPTT for dabigatran). Anti-Xa (for rivaroxaban) and anti-IIa (for dabigatran) activities should however be preferred, expressed in ng/ml with calibrated plasmas (containing predetermined concentration of the tested drug). The half-life is around 8 to 12 hours, with a peak activity 2 to 4 hours after ingestion. Dabigatran is mainly eliminated via the kidney, hence requiring dose-adjustment in case of moderate renal insufficiency, and contra-indicated in case of severe renal insufficiency. Rivaroxaban being excreted via kidney and liver, some precautions should apply in case of liver insufficiency. No data are available in pregnancy or pediatrics, clinical trials are ongoing. There are few interactions with concomitant drugs, which should not be ignored. The short half-life of these new agents compensates for the

  9. Laboratory monitoring of anticoagulation: where do we stand?

    PubMed

    Tripodi, Armando; van den Besselaar, Antonius

    2009-02-01

    The treatment of choice for acute venous thromboembolism is anticoagulant therapy with fast-acting drugs (unfractionated or low-molecular-weight heparin or fondaparinux) aimed at preventing thrombus extension, followed by extended prophylaxis with vitamin K antagonists aimed at preventing recurrence. Experience accumulated over the years has demonstrated that strict laboratory monitoring is required for unfractionated heparin and vitamin K antagonists, making use of these drugs problematic for patients and physicians and prompting researchers to develop new anticoagulants equally effective but without the requirement for laboratory monitoring. The results of clinical trials to date, albeit limited, suggest that these new drugs will probably keep their promise. However, the definitive answer will come subsequent to these clinical trials, when clinicians will start to use these drugs to treat patients in the real world. It is likely that some sort of laboratory monitoring will be required at least for selected categories of patients. Accordingly, clinical laboratories should still be prepared to monitor patients, although the numbers may hopefully decrease sharply in the next decade or so. PMID:19308891

  10. [Anticoagulant rodenticide poisoning in dogs in The Netherlands].

    PubMed

    Robben, J H; Mout, H C; Kuijpers, E A

    1997-09-01

    The occurrence, the diagnosis, and the treatment of anticoagulant rodenticide poisoning in dogs in the Netherlands was evaluated by a survey among Dutch veterinarians carried out by the National Poisons Control Center (NPCC). The survey included information on 54 dogs, 32 being treated by veterinarians who consulted the NPCC and 22 that were admitted to the Utrecht University Clinic for Companion Animals (UUCCA). The poisons that were suspected were brodifacoum (n = 19), bromadiolone (n = 14), difenacoum (n = 8), difethialone (n = 6) and chlorophacinone (n = 1). In 6 dogs the identity of the poison was unknown. Of 31 dogs with hemorrhages, 2 died shortly after presentation to practitioners and 2 died shortly after admission to the UUCCA. Signs of bleeding occurred especially in poisoning by brodifacoum (n = 16). In all but one of the dogs without hemorrhages, the intake of poison had taken place within 24 hours before presentation. The method of treatment varied, with the induction of vomiting and the use of vitamin K mentioned most. The choice of therapy was determined by the length of time after intake of the poison, the clinical signs and whether or not an anticoagulant toxicosis was suspected at the time of the initial examination. These findings provide the basis for discussion of several aspects of diagnosis and treatment. PMID:9534772

  11. Anticoagulative strategies in reconstructive surgery – clinical significance and applicability

    PubMed Central

    Jokuszies, Andreas; Herold, Christian; Niederbichler, Andreas D.; Vogt, Peter M.

    2012-01-01

    Advanced strategies in reconstructive microsurgery and especially free tissue transfer with advanced microvascular techniques have been routinely applied and continously refined for more than three decades in day-to-day clinical work. Bearing in mind the success rates of more than 95%, the value of these techniques in patient care and comfort (one-step reconstruction of even the most complex tissue defects) cannot be underestimated. However, anticoagulative protocols and practices are far from general acceptance and – most importantly – lack the benchmark of evidence basis while the reconstructive and microsurgical methods are mostly standardized. Therefore, the aim of our work was to review the actual literature and synoptically lay out the mechanisms of action of the plethora of anticoagulative substances. The pharmacologic prevention and the surgical intervention of thrombembolic events represent an established and essential part of microsurgery. The high success rates of microvascular free tissue transfer as of today are due to treatment of patients in reconstructive centers where proper patient selection, excellent microsurgical technique, tissue transfer to adequate recipient vessels, and early anastomotic revision in case of thrombosis is provided. Whether the choice of antithrombotic agents is a factor of success remains still unclear. Undoubtedly however the lack of microsurgical experience and bad technique can never be compensated by any regimen of antithrombotic therapy. All the more, the development of consistent standards and algorithms in reconstructive microsurgery is absolutely essential to optimize clinical outcomes and increase multicentric and international comparability of postoperative results and complications. PMID:22294976

  12. Beyond warfarin: The advent of new oral anticoagulants

    PubMed Central

    Laroia, Sandeep T; Morales, Steven; Laroia, Archana T

    2015-01-01

    New oral anticoagulants (NOAC) are the latest addition to anticoagulant armamentarium. Unlike traditional anti-coagulants like warfarin, lab monitoring and management of bleeding complications secondary to these agents is different. As more and more patients are being switched to these drugs, interventional radiologists in particular will benefit from a clinical review of NOAC. PMID:26752818

  13. New versus traditional approaches to oral anticoagulation in patients with atrial fibrillation.

    PubMed

    Reiffel, James A

    2014-04-01

    For clinicians, atrial fibrillation (AFib) is not a disease that will probably be "cured" at some point during their professional lifetime. (online video available at: http://education.amjmed.com/video.php?event_id=445&stage_id=5&vcs=1). AFib is a condition that occurs in association with aging, affecting as many as 1 in 10 patients by the time they reach age 85, and therefore all physicians who read The American Journal of Medicine should be aware of AFib-its etiology, how to recognize it, and with some idea of how it is treated. Perhaps the most important aspect of AFib, however, is as a risk factor for systemic embolism and stroke, which means that almost all patients with AFib will need to receive anticoagulation therapy, probably for the rest of their lives. For the past several decades the only oral anticoagulant agent has been warfarin. Warfarin is an effective anticoagulant, but for many reasons (patient adherence, physician reluctance, warfarin's narrow therapeutic efficacy), less than half of the patients who should be anticoagulated are prescribed warfarin (dropping to less than a third in older patients), and of those who are prescribed and apparently adherent, less than a third maintain serum warfarin levels in the narrow therapeutic range of INR 2-3. Thus, it is clear that the traditional prescription of warfarin for patients with AFib has failed to meet an important need for reducing risk of systemic embolism and stroke. Fortunately, however, within the last couple of years a new generation of novel oral anticoagulant (NOAC) agents has proven successful in randomized clinical trials and has been passing through the regulatory approval process. For physicians this represents both a challenge-to learn and understand the evidence base for these new anticoagulant therapies-and the opportunity now to treat their aging patients who are increasingly likely to present with cerebrovascular disease risks and who are depending on their physicians to treat them

  14. Fulminant phlegmasia cerulea dolens with concurrent cholangiocarcinoma and a lupus anticoagulant: a case report and review of the literature.

    PubMed

    Chang, Grace; Yeh, James J

    2014-07-01

    Phlegmasia cerulea dolens (PCD) is an aggressive and life-threatening form of venous thrombosis complicated by ischemic necrosis. Massive thrombosis extends to collateral veins resulting in venous congestion with fluid sequestration in the interstitium causing collapse of arterioles, which progresses to ischemia and, if severe, circulatory collapse and shock. The mortality rate for PCD is as high as 40%, especially when gangrene develops. PCD has been associated with acquired thrombophilias, including malignancy and antiphospholipid syndrome (APS). We present a unique case of a patient with PCD refractory to anticoagulant and thrombolytic therapy, whose fulminant course was attributed to concurrent cholangiocarcinoma and antiphospholipid antibodies identified by a positive lupus anticoagulant assay. This case highlights the importance of uncovering precipitating causes of thromboembolism, which may offer prognostic information and may necessitate therapy beyond anticoagulation and thrombolysis to reduce the morbidity of PCD. The current literature on PCD and APS, along with their associations with malignancy, is reviewed. PMID:24553060

  15. Laboratory determination of old and new targeted anticoagulant agents for prevention of bleeding and thrombotic events in cancer patients.

    PubMed

    Harenberg, Job

    2016-04-01

    A two-fold prolongation of activated partial thromboplastin time (APTT) is established as therapeutic range for therapy with unfractionated heparin, hirudin and argatroban. The international normalized ratio (INR) of 2 to 3 is required to maintain anticoagulation in the therapeutic range of vitamin K antagonists. The therapeutic range of anti-factor Xa activity during therapy with low-molecular weight heparins and danaparoid are less well and of direct oral anticoagulants (DOAC) poorly defined. The relation of aPTT and INR values to thrombotic and bleeding events are well established despite a large variation of values in affected patients. The relation of coagulation values of the other anticoagulants to clinical events is open. The value of determination in cancer patients is higher because of the increased risk for thrombotic and bleeding events of this patient group. Several activities are currently undertaken to certify methods for in vitro diagnostic testing for DAOCs. PMID:27067972

  16. Antiplatelet and anticoagulation agents in acute coronary syndromes: what is the current status and what does the future hold?

    PubMed

    Huber, Kurt; Bates, Eric R; Valgimigli, Marco; Wallentin, Lars; Kristensen, Steen Dalby; Anderson, Jeffrey L; Lopez Sendon, Jose Luis; Tubaro, Marco; Granger, Christopher B; Bode, Christoph; Ohman, Erik Magnus; Steg, Philippe Gabriel

    2014-11-01

    Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y12 receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio. PMID:25440788

  17. Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring?

    PubMed

    Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla

    2014-10-01

    The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo. PMID:24919144

  18. Management of dental extraction in patients undergoing anticoagulant treatment. Results from a large, multicentre, prospective, case-control study.

    PubMed

    Bacci, Christian; Maglione, Michele; Favero, Lorenzo; Perini, Alessandro; Di Lenarda, Roberto; Berengo, Mario; Zanon, Ezio

    2010-11-01

    Following favourable results from a previous study, a large, multicentre, prospective, case-control study was performed to further assess the incidence of bleeding complications after dental extraction in patients taking oral anticoagulant therapy (OAT). Four hundred fifty-one patients being treated with warfarin who required dental extraction were compared with a control group of 449 non-anticoagulated subjects undergoing the same procedure. In the warfarin-treated group, the oral anticoagulant regimen was maintained unchanged, such that the patients had an International Normalised Ratio ranging between 1.8 and 4, and local haemostatic measures (i.e. fibrin sponges, silk sutures and gauzes saturated with tranexamic acid) were adopted. All the procedures were performed in an outpatient setting. Seven bleeding complications occurred in the OAT group and four in the control group; the difference in the number of bleeding events between the two groups was not statistically significant (OR=1.754; 95% CI 0.510 - 6.034; p=0.3727). No post-operative late bleeds requiring hospitalisation and/or blood transfusions were recorded, and the adjunctive local haemostatic measures were adequate to stop the bleeding. The results of our protocol applied in this large, multicenter study show that dental extractions can be performed easily and safely in anticoagulated outpatients without any modification of the ongoing anticoagulant therapy, thus minimising costs and reducing discomfort for patients. PMID:20806110

  19. Cerebrovascular Accident due to Thyroid Storm: Should We Anticoagulate?

    PubMed Central

    Gonzalez-Rivera, Alexis; Coste-Sibilia, Santiago

    2016-01-01

    Thyroid storm is a life-threatening condition that occurs secondary to an uncontrolled hyperthyroid state. Atrial fibrillation is a cardiovascular complication occurring in up to 15% of patients experiencing thyroid storm, and if left untreated this condition could have up to a 25% mortality rate. Thyroid storm with stroke is a rare presentation. This case report details a left middle cerebral artery (MCA) stroke with global aphasia and thyroid storm in a 53-year-old Hispanic male patient. Although uncommon, this combination has been reported in multiple case series. Although it is well documented that dysfunctional thyroid levels promote a hypercoagulable state, available guidelines from multiple entities are unclear on whether anticoagulation therapy is appropriate in this situation. PMID:27597905

  20. Noncompaction and embolic myocardial infarction: the importance of oral anticoagulation.

    PubMed

    Pulignano, Giovanni; Tinti, Maria Denitza; Tolone, Stefano; Musto, Carmine; De Lio, Lucia; Pino, Paolo Giuseppe; Minardi, Giovanni; Violini, Roberto; Uguccioni, Massimo

    2015-01-01

    Left ventricular noncompaction (LVNC) is characterized by left ventricular (LV) hypertrabeculations and is associated with heart failure, arrhythmias and embolism. We report the case of a 67-year-old LVNC patient, under oral anticoagulation (OAC) therapy for apical thrombosis. After she discontinued OAC, the thrombus involved almost the whole of the left ventricle; in a few months her condition worsened, requiring hospitalization, and despite heparin infusion she experienced myocardial infarction (MI), caused by embolic occlusion of the left anterior descending artery. Although infrequent as a complication of LVNC, and usually attributable to microvascular dysfunction, in this case MI seems due to coronary thromboembolism from dislodged thrombotic material in the left ventricle. PMID:26162290

  1. Use of anticoagulants in elderly patients: practical recommendations

    PubMed Central

    Robert-Ebadi, Helia; Le Gal, Grégoire; Righini, Marc

    2009-01-01

    Elderly people represent a patient population at high thromboembolic risk, but also at high hemorrhagic risk. There is a general tendency among physicians to underuse anticoagulants in the elderly, probably both because of underestimation of thromboembolic risk and overestimation of bleeding risk. The main indications for anticoagulation are venous thromboembolism (VTE) prophylaxis in medical and surgical settings, VTE treatment, atrial fibrillation (AF) and valvular heart disease. Available anticoagulants for VTE prophylaxis and initial treatment of VTE are low molecular weight heparins (LMWH), unfractionated heparin (UFH) or synthetic anti-factor Xa pentasaccharide fondaparinux. For long-term anticoagulation vitamin K antagonists (VKA) are the first choice and only available oral anticoagulants nowadays. Assessing the benefit-risk ratio of anticoagulation is one of the most challenging issues in the individual elderly patient, patients at highest hemorrhagic risk often being those who would have the greatest benefit from anticoagulants. Some specific considerations are of utmost importance when using anticoagulants in the elderly to maximize safety of these treatments, including decreased renal function, co-morbidities and risk of falls, altered pharmacodynamics of anticoagulants especially VKAs, association with antiplatelet agents, patient education. Newer anticoagulants that are currently under study could simplify the management and increase the safety of anticoagulation in the future. PMID:19503778

  2. Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True?

    PubMed Central

    Violi, Francesco; Lip, Gregory YH; Pignatelli, Pasquale; Pastori, Daniele

    2016-01-01

    Abstract Educational advice is often given to patients starting treatment with vitamin K Antagonists (VKAs). A great emphasis is made on nutritional information. Common belief is that dietary vitamin K intake could counteract the anticoagulant effect by VKAs and for many years, patients have been discouraged to consume vitamin-K-rich foods, such as green leafy vegetables. The objective of this study is to summarize the current evidence supporting the putative interaction between dietary vitamin K intake and changes in INR with the VKAs. Data sources are MEDLINE via PubMed and Cochrane database. All clinical studies investigating the relationship between dietary vitamin K and measures of anticoagulation were included. We excluded all studies of supplementation of vitamin K alone. We performed a systematic review of the literature up to October 2015, searching for a combination of “food,” “diet,” “vitamin K,” “phylloquinone,” “warfarin,” “INR,” “coagulation,” and “anticoagulant.” Two dietary interventional trials and 9 observational studies were included. We found conflicting evidence on the effect of dietary intake of vitamin K on coagulation response. Some studies found a negative correlation between vitamin K intake and INR changes, while others suggested that a minimum amount of vitamin K is required to maintain an adequate anticoagulation. Median dietary intake of vitamin K1 ranged from 76 to 217 μg/day among studies, and an effect on coagulation may be detected only for high amount of vitamin intake (>150 μg/day). Most studies included patients with various indications for VKAs therapy, such as atrial fibrillation, prosthetic heart valves, and venous thromboembolism. Thus, INR target was dishomogeneous and no subanalyses for specific populations or different anticoagulants were conducted. Measures used to evaluate anticoagulation stability were variable. The available evidence does not support current advice to modify

  3. Updates in the perioperative and emergency management of non-vitamin K antagonist oral anticoagulants.

    PubMed

    Faraoni, David; Levy, Jerrold H; Albaladejo, Pierre; Samama, Charles-Marc

    2015-01-01

    Perioperative management of patients treated with the non-vitamin K antagonist oral anticoagulants is an ongoing challenge. Due to the lack of good clinical studies involving adequate monitoring and reversal therapies, management requires knowledge and understanding of pharmacokinetics, renal function, drug interactions, and evaluation of the surgical bleeding risk. Consideration of the benefit of reversal of anticoagulation is important and, for some low risk bleeding procedures, it may be in the patient's interest to continue anticoagulation. In case of major intra-operative bleeding in patients likely to have therapeutic or supra-therapeutic levels of anticoagulation, specific reversal agents/antidotes would be of value but are currently lacking. As a consequence, a multimodal approach should be taken which includes the administration of 25 to 50 U/kg 4-factor prothrombin complex concentrates or 30 to 50 U/kg activated prothrombin complex concentrate (FEIBA®) in some life-threatening situations. Finally, further studies are needed to clarify the ideal therapeutic intervention. PMID:25925382

  4. Adherence in outpatients taking warfarin and its effect on anticoagulation control in Jordan.

    PubMed

    Ababneh, Mera A; Al-Azzam, Sayer I; Alzoubi, Karem H; Rababa'h, Abeer M

    2016-08-01

    Background Medication adherence is an important element for the success of any therapeutic plan. The picture is more complicated with warfarin, due to its small therapeutic window and patients' needs to have effective anticoagulation control. Objective To measure warfarin-adherence, warfarin-knowledge and to assess the relationship between adherence and anticoagulation control. Setting Adult outpatients (≥18 years) taking warfarin at two medical sites in north of Jordan were invited to participate. Method This was a cross sectional study in which survey questionnaire that included demographic, clinical, warfarin related questions and Morisky Medication Adherence Scale (MMAS-8) was administered to patients in Arabic language. International normalization ratio (INR) readings were retrieved from patients' medical records. Main outcome measure MMAS-8 adherence scores and time within therapeutic range were calculated. Results More than half of study participants (54 %) were adherent (MMAS-8 = 8). The MMAS-8 adherence scores were significantly associated with warfarin-knowledge scores (Spearman's ρ = 0.291, p = 0.000). Adherent patients were more likely to have good anticoagulation control compared to non-adherent patients (MMAS-8 ≤ 7). Conclusion Adherence to warfarin therapy can have a substantial effect on anticoagulation control. Thus, healthcare practitioners should consider strategies to improve patient adherence to warfarin. PMID:27015937

  5. [Drug therapy in interventional radiology].

    PubMed

    Sumkauskaite, M; Bryant, M; Kortes, N; Stampfl, U; Radeleff, B

    2015-06-01

    In the context of pre-interventional drug therapy, a premedication is given to patients who are known to have an allergy to contrast media, have renal impairment or hyperthyroidism. An already existing anticoagulation therapy, in anticipation of the planned intervention, must be reviewed and changed or even suspended as required. For peri-interventional drug therapy it is important to consider how strenuous the procedure will be as well as the general condition of the patient. Further discussion with anesthetists may be required for the planning of pain therapy or sedation during the procedure. These factors help to ensure maximum patient comfort as well as the success of the intervention. Post-interventional anticoagulation therapy, usually started peri-interventionally, plays an important role in minimizing the risk of acute thrombosis as well as in maintaining long-term functioning of the implanted material. The form of the anticoagulation therapy is set according to the type of intervention. PMID:26063076

  6. Antithrombotic Therapy for Atrial Fibrillation

    PubMed Central

    You, John J.; Singer, Daniel E.; Howard, Patricia A.; Lane, Deirdre A.; Eckman, Mark H.; Fang, Margaret C.; Hylek, Elaine M.; Schulman, Sam; Go, Alan S.; Hughes, Michael; Spencer, Frederick A.; Manning, Warren J.; Halperin, Jonathan L.

    2012-01-01

    Background: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS2 score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS2 score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized

  7. New Oral Anticoagulants vs Vitamin K Antagonists: Benefits for Health-Related Quality of Life in Patients with Atrial Fibrillation

    PubMed Central

    Alegret, Josep M.; Viñolas, Xavier; Arias, Miguel A.; Martínez-Rubio, Antoni; Rebollo, Pablo; Ràfols, Carles; Martínez-Sande, José L.

    2014-01-01

    New oral anticoagulants (NOAC) have demonstrated their efficacy as an alternative to vitamin K antagonists (VKA) in the prophylaxis of cardioembolic events in patients with atrial fibrillation (AF). However, evidence on the benefits of NOAC in health-related quality of life (HRQoL) is lacking.We evaluated changes in HRQoL related to oral anticoagulation therapy employing a specific questionnaire in a cohort of 416 patients with AF undergoing electrical cardioversion. In terms of HRQoL, we observed a progressive adaptation to treatment with VKA; satisfaction with NOAC remained constant. Older age, higher left ventricular ejection fraction and NOAC were associated with better HRQoL. PMID:24843316

  8. New oral anticoagulants vs vitamin K antagonists: benefits for health-related quality of life in patients with atrial fibrillation.

    PubMed

    Alegret, Josep M; Viñolas, Xavier; Arias, Miguel A; Martínez-Rubio, Antoni; Rebollo, Pablo; Ràfols, Carles; Martínez-Sande, José L

    2014-01-01

    New oral anticoagulants (NOAC) have demonstrated their efficacy as an alternative to vitamin K antagonists (VKA) in the prophylaxis of cardioembolic events in patients with atrial fibrillation (AF). However, evidence on the benefits of NOAC in health-related quality of life (HRQoL) is lacking.We evaluated changes in HRQoL related to oral anticoagulation therapy employing a specific questionnaire in a cohort of 416 patients with AF undergoing electrical cardioversion. In terms of HRQoL, we observed a progressive adaptation to treatment with VKA; satisfaction with NOAC remained constant. Older age, higher left ventricular ejection fraction and NOAC were associated with better HRQoL. PMID:24843316

  9. Primary Care Atrial Fibrillation Service: outcomes from consultant-led anticoagulation assessment clinics in the primary care setting in the UK

    PubMed Central

    Das, Moloy; Panter, Lee; Wynn, Gareth J; Taylor, Rob M; Connor, Neil; Mills, Joseph D; Kirchhof, Paulus; Gupta, Dhiraj

    2015-01-01

    Objective Stroke-risk in atrial fibrillation (AF) can be significantly reduced by appropriate thromboembolic prophylaxis. However, National Institute for Health and Care Excellence estimates suggest that up to half of eligible patients with AF are not anticoagulated, with severe consequences for stroke prevention. We aimed to determine the outcome of an innovative Primary Care AF (PCAF) service on anticoagulation uptake in a cohort of high-risk patients with AF in the UK. Methods The PCAF service is a novel cooperative pathway providing specialist resources within general practitioner (GP) practices. It utilises a four-phase protocol to identify high-risk patients with AF (CHA2DS2-VASc ≥1) who are suboptimally anticoagulated, and delivers Consultant-led anticoagulation assessment within the local GP practice. We assessed rates of anticoagulation in high-risk patients before and after PCAF service intervention, and determined compliance with newly-initiated anticoagulation at follow-up. Results The PCAF service was delivered in 56 GP practices (population 386 624; AF prevalence 2.1%) between June 2012 and June 2014. 1579 high-risk patients with AF with suboptimal anticoagulation (either not taking any anticoagulation or taking warfarin but with a low time-in-therapeutic-range) were invited for review, with 86% attending. Of 1063 eligible patients on no anticoagulation, 1020 (96%) agreed to start warfarin (459 (43%)) or a non-vitamin K antagonist oral anticoagulant (NOAC, 561 (53%)). The overall proportion of eligible patients receiving anticoagulation improved from 77% to 95% (p<0.0001). Additionally, 111/121 (92%) patients suboptimally treated with warfarin agreed to switch to a NOAC. Audit of eight practices after 195 (185–606) days showed that 90% of patients started on a new anticoagulant therapy had continued treatment. Based on data extrapolated from previous studies, around 30–35 strokes per year may have been prevented in these previously under

  10. Factor V anticoagulants: clinical, biochemical, and immunological observations

    PubMed Central

    Feinstein, Donald I.; Rapaport, Samuel I.; McGehee, William G.; Patch, Mary Jane

    1970-01-01

    A patient who had received multiple transfusions for complications of acute hemorrhagic pancreatitis developed a potent factor V anticoagulant with bleeding due to defective hemostasis. Despite its potency, the anticoagulant disappeared within 15 days of its first manifestation. A second patient with adenocarcinoma of the colon developed an anticoagulant to factor V postoperatively after a single blood transfusion. The anticoagulants appeared to react stoichiometrically with factor V in normal plasma in vitro. They had the physicochemical properties of immunoglobulins, and their activity was neutralized by antihuman immunoglobulin antiserum. One anticoagulant appeared to be slightly more active against homologous than against autologous factor V, but it also inhibited heterologous factor V. Both anticoagulants progressively inactivated intrinsic prothrombin activator formed from normal reagents in the incubation mixture of the thromboplastin generation test, thus confirming that factor V is required for the effective action of the intrinsic prothrombin activator. Since the anticoagulants were immunoglobulins whose activity was consumed in their reaction with factor V, consumption of anticoagulant activity was used to detect factor V antigenic material in test materials. Human serum without factor V clotting activity was found to consume anticoagulant activity, i.e., to contain inactive factor V antigenic material. Plasma from two patients with hereditary factor V deficiency (parahemophilia) failed to consume significant anticoagulant activity. Thus, the lack of factor V activity in these patients represents a deficiency of factor V molecules rather than the synthesis of a defective molecule with impaired clotting activity. PMID:4194089

  11. The laboratory's 2015 perspective on direct oral anticoagulant testing.

    PubMed

    Gosselin, R C; Adcock, D M

    2016-05-01

    The introduction of direct oral anticoagulant (DOAC) therapy into clinical use in the past 5 years has had significant impact on the clinical laboratory. Clinicians' desire to determine plasma drug presence or measure drug concentration, and more recent observations regarding the limitations and utility of coagulation testing in the setting of DOAC treatment, suggest that early published recommendations regarding laboratory testing should be reassessed. These initial recommendations, furthermore, were often based on drug-spiked plasma studies, rather than samples from patients receiving DOAC therapy. We have demonstrated that reagent sensitivity varies significantly whether drug-spiked samples or samples from DOAC-treated patients are tested. Data from drug-enriched samples must therefore be interpreted with caution or be used as a guide only. We present laboratory assays that can be used to determine drug presence and to measure drug concentration, and provide recommended testing algorithms. As DOAC therapy may significantly impact on specialty coagulation assays, we review those tests with the potential to give false-positive and false-negative results. PMID:26791879

  12. [New oral anticoagulants: from theory to practice].

    PubMed

    de Moerloose, P; Casini, A; Boehlen, F; Fontana, P

    2013-01-16

    Physicians are confronted with many new antithrombotic drugs, either antiplatelet agents or new oral anticoagulants (NOAC). Targets of NOAC are specific (either anti-IIa or antiXa) and clinical studies have shown that NOAC are as efficacious and as safe as "old" anticoagulants (heparin, low molecular weight heparin, vitamin K antagonists); moreover they present some advantages. Indeed, NOAC have a wide therapeutic window and do not require laboratory monitoring. Therefore, it is very tempting to prescribe them on a large scale basis in patients at risk or having thromboembolic diseases. However, things are not so simple in the day-to-day practice and this review aims at answering in a brief and simplified manner to some questions. PMID:23409645

  13. Lupus anticoagulants: pathogenesis and laboratory diagnosis.

    PubMed

    Court, E L

    1997-12-01

    The pathogenesis of the lupus anticoagulant (LA) has been the focus of much research over the past decade, and a plethora of laboratory tests have been developed to detect it. This essay reviews the nature of LA and its pathogenesis, and a number of approaches employed in its diagnosis. These range from well established tests such as the kaolin clotting time (KCT), activated partial thromboplastin time (APTT) and tissue thromboplastin inhibition test (TTI), to the 'newer' tests such as the dilute Russell's viper venom time (DRVVT) and more recent snake venom tests such as the textarin/ecarin ratio and Taipan snake venom time (TSVT). The criteria for diagnosis are discussed, including pre-analytical variables such as sample preparation, and the effects of therapeutic anticoagulants used to treat thrombotic manifestations of the syndrome or an underlying disease process. PMID:9624740

  14. Anticoagulation reversal in the era of the non-vitamin K oral anticoagulants.

    PubMed

    Enriquez, Andres; Lip, Gregory Y H; Baranchuk, Adrian

    2016-07-01

    In recent years, non-vitamin K oral anticoagulants (NOACs) have emerged as an alternative to warfarin for the prevention and treatment of thrombo-embolic disease. Large randomized trials have demonstrated that these agents, which act by directly targeting thrombin (dabigatran) and factor Xa (rivaroxaban, apixaban, and edoxaban), are at least as effective as warfarin, with lower rates of bleeding and fewer interactions with food and drugs. In addition, NOACs have a more predictable anticoagulant effect, allowing a fixed dose regimen and obviating the need for routine anticoagulation monitoring. Since the introduction of NOACs, one of the major concerns for clinicians has been the lack of specific agents to reverse their anticoagulant effect in case of life-threatening haemorrhagic complications or emergency surgery, which have limited their use in patients deemed at a higher risk of bleeding. New specific antidotes (e.g. idarucizumab, andexanet alfa, and ciraparantag) show promising data, and may soon become available for clinical use. In this article, we review the pharmacology of these agents, the incidence and outcomes of haemorrhagic complications, the available strategies for anticoagulation reversal, and the more recent advances for the development of specific antidotes. PMID:25816811

  15. Reduced Anticoagulant Effect of Dabigatran in a Patient Receiving Concomitant Phenytoin.

    PubMed

    Wiggins, Barbara S; Northup, Amanda; Johnson, Dominic; Senfield, Jeffrey

    2016-02-01

    Dabigatran, a direct thrombin inhibitor, is an oral anticoagulant indicated for the prevention of stroke in patients with atrial fibrillation (AF) and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. Dabigatran, as well as the other new anticoagulants-rivaroxaban, apixaban, and edoxaban-are substrates for P-glycoprotein (P-gp). Although the U.S. labeling for rivaroxaban and apixaban states to avoid concomitant use with phenytoin, a known P-gp inducer, the U.S. labeling for dabigatran and edoxaban are less clear. We describe the first case report, to our knowledge, documenting a drug interaction between phenytoin and dabigatran by using laboratory measurements of dabigatran serum concentrations. A 45-year-old African-American man was admitted to the inpatient cardiology service following defibrillations from his implantable cardioverter defibrillator. The patient was evaluated and received appropriate antitachycardia pacing for atrial tachyarrhythmias for an episode of ventricular tachycardia (VT), and antiarrhythmic therapy with sotalol was initiated to reduce both his AF and VT burden. On review of the patient's medications for potential interactions, it was discovered that the patient was taking both dabigatran and phenytoin. To determine the magnitude of this drug interaction prior to making a change in his anticoagulation regimen, a dabigatran serum concentration was measured. This concentration was undetectable, indicating that phenytoin had a significant influence on dabigatran's metabolism and that this patient was at high risk for stroke. Clinicians should be aware of this interaction between phenytoin and dabigatran as well as with all other new oral anticoagulants. In patients taking phenytoin who require an anticoagulant, only warfarin should be prescribed to minimize the risk of stroke. In addition, the prescribing information for dabigatran should be updated to include other medications that result in a significant

  16. New oral anticoagulants: not quite there yet.

    PubMed

    Karthikeyan, Ganesan; Eikelboom, John W; Hirsh, Jack

    2009-01-01

    The results of 3 large randomized trials of activated factor X inhibitors, for the prevention of venous thromboembolism, recently became available. Similar data for orally active thrombin inhibitors is also available from recent trials. In this review, we attempt to provide a balanced perspective on the relative merits and demerits of the new, orally active anticoagulants, and speculate on the future of these agents in clinical practice. PMID:19341179

  17. Novel anticoagulants in atrial fibrillation stroke prevention

    PubMed Central

    DiNicolantonio, James J; Topping, Taylor J; Wee, Benjamin

    2012-01-01

    This review article evaluates novel oral anticoagulants in comparison with warfarin for thromboembolism prophylaxis in patients with atrial fibrillation (AF). AF is the most frequently diagnosed arrhythmia in the United States. The most serious side effect of AF is stroke. Warfarin has several decades of proven efficacy in AF-related stroke prevention but the drug’s numerous drawbacks make its implementation difficult for practitioners and patients. The difficulties of warfarin have prompted the development of alternative anticoagulants for AF-related stroke prevention with better efficacy, safety, and convenience. The oral direct thrombin inhibitor, dabigatran, and the oral factor Xa inhibitors, rivaroxaban and apixaban, have been evaluated in a large phase III trial. Dabigatran, rivaroxaban and apixaban were shown to be noninferior compared with warfarin in the prevention of stroke. Dabigatran and apixaban were found to be statistically superior to warfarin. All three may also have a better safety profile than warfarin. In conclusion, novel anticoagulants have a different pharmacologic profile compared with warfarin that may eliminate many of the treatment inconveniences. Practitioners must also be aware of the disadvantages these new drugs possess when choosing a management strategy for their patients. Drug selection may become clearer as these new drugs are used more extensively. PMID:23251773

  18. New developments in anticoagulation for atrial fibrillation.

    PubMed

    Usman, M Haris U; Notaro, Lawrence A; Patel, Harsh; Ezekowitz, Michael D

    2008-09-01

    The incidence of stroke in patients with atrial fibrillation (AF) is five times greater than that in age-matched controls. Warfarin reduces this incidence by two thirds and is the most effective agent for this indication. However, despite its efficacy, warfarin management is tedious and is useful only in a subsegment of the population who needs anticoagulation and has no contraindications. Many agents are poised to replace warfarin as an effective anticoagulant for stroke prevention in AF. The direct thrombin inhibitor dabigatran is furthest along in clinical development, followed by the factor Xa inhibitors rivaroxaban and apixaban. All these agents seem effective, and none appears mechanistically superior over another. Dabigatran's advantage is that it was tested in two dosages in a phase 3 evaluation based on earlier phase 2 studies in patients with AF, whereas dosage data for the other agents were extrapolated from phase 2 programs for venous thromboembolism prevention. The vitamin K antagonist ATI-5923 offers clinical benefits similar to warfarin's, but with no or fewer drug-drug interactions, potentially greater time in therapeutic range, and probably less need for dose adjustment and laboratory monitoring. It challenges the newer mechanistic agents in efficacy and raises the bar for comparison in future head-to-head trials. Further analysis and clinical trial testing are still needed to determine whether one or all of these agents are effective anticoagulants for stroke prevention in patients with AF. PMID:18814828

  19. Novel oral anticoagulants in plastic surgery.

    PubMed

    Munson, C F; Reid, A J

    2016-05-01

    Novel oral anticoagulants (NOACs) have emerged as a good alternative to warfarin in the prevention of stroke for patients with atrial fibrillation. NOAC use is increasing rapidly; therefore, greater understanding of their use in the perioperative period is important for optimal care. Studies and reviews that reported on the use of NOACs were identified, with particular focus on the perioperative period. PubMed was searched for relevant articles published between January 2000 and August 2015. The inevitable rise in the use of NOACs such as rivaroxaban (Xarelto™), apixaban (Eliquis™), edoxaban (Lixiana™) and dabigatran (Pradaxa™) may present a simplified approach to perioperative anticoagulant management due to fewer drug interactions, rapidity of onset of action and relatively short half-lives. Coagulation status, however, cannot reliably be monitored and no antidotes are currently available. When planning for discontinuation of NOACs, special consideration of renal function is required. Advice regarding the management of bleeding complications is provided for consideration in emergency surgery. In extreme circumstances, haemodialysis may be considered for bleeding with the use of dabigatran. NOACs will increasingly affect operative planning in plastic surgery. In order to reduce the incidence of complications associated with anticoagulation, the management of NOACs in the perioperative period requires knowledge of the time of last dose, renal function and the bleeding risk of the planned procedure. Consideration of these factors will allow appropriate interpretation of the current guidelines. PMID:27013144

  20. [New orally anticoagulants and brain stroke].

    PubMed

    Kaczorowska, Beata; Pawełczyk, Małgorzata; Przybyła, Monika

    2016-05-01

    Brain stroke is a grave society problem. About 20% ischemic strokes are cardiac related problems. Atrial fibrillation (AF) is the most common cause of ischemic strokes. Decision to deploy anticoagulant treatment with AF patient depends on bleeding and thrombo-embolic risk which summerise scale CHA(2)DS(2)VASc and HAS-BLED. Past recent years in AF treatment anticoagulants from the group of vitamin K antagonist were used. At present in brain stroke prevention and systemic emboilment, new oral anticoagulants (NOA) which weren't worst than vitamin K antagonists, and they are recomendet in most cases of AF unrelated with heart valve defets. Useing NOA causes lower risk of bleeding, including intracranial heamorrhage. It is believed that this is related to the selective inhibition of specific coagulation factors, and respect other hemostatic mechanisms. Results from clinical studies NOA are encouraging, but still lacks clear answers regarding, among other things: long-term safety of treatment and economically viable in everyday clinical practice. In addition, to date there is no specific antidote for this group of drugs. PMID:27234866

  1. EDUC’AVK: Reduction of Oral Anticoagulant-related Adverse Events After Patient Education: A Prospective Multicenter Open Randomized Study

    PubMed Central

    Labarère, José; Yver, Jacqueline; Satger, Bernadette; Allenet, Benoit; Berremili, Touffek; Fontaine, Michèle; Franco, Guy; Bosson, Jean Luc

    2008-01-01

    Background Long-term oral anticoagulation treatment is associated with potential morbidity. Insufficient patient education is linked to poorly controlled anticoagulation. However the impact of a specific educational program on anticoagulation related morbidity remains unknown. Objective To evaluate the effect of an oral anticoagulation patient education program in reducing both hemorrhagic and recurrent thrombotic complications. Design/Participants We conducted a prospective, multicenter open randomized study, comparing an interventional group who received a specific oral anticoagulation treatment educational program with a control group. Eligible patients were older than 18 and diagnosed as having deep vein thrombosis or pulmonary embolism requiring therapy with a vitamin K antagonist for 3 months or more. Our primary outcome was the occurrence of hemorrhagic or thromboembolic events. Results During the 3-month follow-up the main outcome criteria were observed 20 times (6.6% of patients), 5 (3.1%) in the experimental and 15 (10.6%) in the control group. Consequently, in multivariate analysis, the cumulative risk reduction in the experimental group was statistically significant (OR 0.25, 95% CI 0.1 – 0.7,  < 0.01). Conclusions Patient education using an educational program reduced VKA-related adverse event rates. PMID:18566863

  2. Review of the Target-Specific Oral Anticoagulants in Development for the Treatment and Prevention of Venous Thromboembolism.

    PubMed

    Devabhakthuni, Sandeep; Yoon, Connie H; Pincus, Kathleen J

    2016-08-01

    Anticoagulation therapy is often indicated for the treatment and prevention of venous thromboembolism (VTE). Despite advances in anticoagulant management with parenteral anticoagulants and vitamin K antagonists, limitations to their use still exists, leading to investigation of alternative anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors. To date, 3 target-specific oral anticoagulants (TSOACs) are Food and Drug Administration approved; several other agents are currently in development to optimize VTE management and minimize bleeding risks. The objective of this systematic review article is to provide clinicians an overview of the clinical evidence on the investigational TSOACs for the treatment and prevention of VTE. Of the agents in development, edoxaban holds the most promise due to robust data supporting its clinical benefit with a similar bleeding risk to currently approved agents. Clinicians should understand the TSOACs under investigation, since differences in pharmacokinetics and pharmacodynamics may influence clinical decision making and agent selection for management of VTE. Currently, no direct comparisons between TSOACs have been conducted. Agents under investigation have yet to overcome the major limitations of the currently existing TSOACs. Further studies are necessary to clarify which TSOAC agent is best for management of VTE in clinical practice. PMID:25634013

  3. Perioperative Management of Anticoagulation-Review of Latest Evidence.

    PubMed

    Kannan, Arun; Poongkunran, Chithra; Shenoy, Sundeep; Abidov, Aiden

    2016-01-01

    Periprocedural anticoagulation bridging is recommended to reduce the risk of thromboembolic events in patients at a higher risk of developing thromboembolism during the perioperative period. The optimal periprocedural anticoagulation strategy has not been established. Unfractionated heparin and low molecular heparin are used in preventing thromboembolism in the special population. Novel oral anticoagulants that directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are shown as effective anticoagulants in preventing thromboembolism (venous thromboembolism) in various medical conditions. They have the advantage of having a faster onset, shorter half-lives, easier monitoring, and predicable doses. But there are disadvantages to newer anticoagulants such as the unavailability of definitive reversal agents and lack of data in patients with renal insufficiency. We review the latest evidence on the effects of newer oral anticoagulants in preventing thromboembolism and its bleeding risks. PMID:26214205

  4. Personalizing oral anticoagulant treatment in patients with atrial fibrillation.

    PubMed

    Capranzano, Piera; Miccichè, Eligio; D'Urso, Lucia; Privitera, Fiorella; Tamburino, Corrado

    2013-08-01

    For decades, warfarin has remained the standard oral anticoagulation for stroke prevention in atrial fibrillation (AF). Three novel oral anticoagulants (NOACs) have been recently approved for stroke prevention in non-valvular AF: dabigatran, rivaroxaban and apixaban. Better pharmacological and clinical profiles make these newcomers a preferable alternative over warfarin. Current AF guidelines do not endorse NOACs over warfarin, or one NOAC over another. Indeed, choice of the anticoagulation regimen should be personalized based on the relative efficacy and safety of different agents across subgroups stratified by thrombotic and bleeding risk, as well as on other clinical factors, including anticoagulation control on warfarin, drug interactions, compliance and need for coagulation monitoring. This review appraises i) the randomized evidence on approved NOACs versus warfarin in AF across subgroups stratified by risk factors of stroke and bleeding and by the anticoagulation level reached on warfarin; and ii) clinical factors impacting on the anticoagulation regimen selection. PMID:23957907

  5. Approach to the new oral anticoagulants in family practice

    PubMed Central

    Douketis, James; Bell, Alan David; Eikelboom, John; Liew, Aaron

    2014-01-01

    Abstract Objective To compare key features of the new oral anticoagulants (NOACs)—dabigatran, rivaroxaban, and apixaban—and to address questions that arise when comparing the NOACs. Sources of information PubMed was searched for recent (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for stroke prevention in atrial fibrillation (AF) and for the treatment of acute venous thromboembolism (VTE). Main message All NOACs are at least as effective as warfarin for stroke prevention in patients with nonvalvular AF, and are at least as safe in terms of bleeding risk according to 3 large trials. Meta-analyses of these trials have shown that, compared with warfarin therapy, NOACs reduced total mortality, cardiovascular mortality, and intracranial bleeding, and there was a trend toward less overall bleeding. Practical advantages of NOACs over warfarin include fixed once- or twice-daily oral dosing without the need for coagulation monitoring, and few known or defined drug or food interactions. Potential drawbacks of NOACs include a risk of bleeding that might be increased in patients older than 75 years, increased major gastrointestinal bleeding with high-dose dabigatran, increased dyspepsia with dabigatran, the lack of a routine laboratory test to reliably measure anticoagulant effect, and the lack of an antidote for reversal. No direct comparisons of NOACs have been made in randomized controlled trials, and the choice of NOAC is influenced by individual patient characteristics, including risk of stroke or VTE, risk of bleeding, and comorbidity (eg, renal dysfunction). Conclusion The NOACs represent important alternatives in the management of patients with AF and VTE, especially for patients who have difficulty accessing regular coagulation monitoring. The companion to this article addresses common “what if” questions that arise in the long-term clinical follow-up and management of patients receiving NOACs. PMID:25392438

  6. Non-vitamin K antagonist oral anticoagulants for the prevention of recurrent venous thromboembolism.

    PubMed

    Bauersachs, Rupert

    2016-08-01

    Venous thromboembolism (VTE) is associated with a risk of recurrence that depends on factors specific to index event and patient. A first unprovoked VTE increases the risk of a recurrent event, particularly during the first year after anticoagulation cessation. Determining a strategy for the long-term prevention of recurrent VTE poses challenges that stem from a lack of agreement on recommended therapy duration and varying treatment burden for the patient. Oral anticoagulants, including vitamin K antagonists and non-vitamin K antagonist oral anticoagulants (NOACs), are the main treatment options for the long-term prevention of recurrent VTE. However, the risk of VTE recurrence must be balanced against the risk of bleeding in each patient. Phase III clinical trials have evaluated rivaroxaban, apixaban and dabigatran for extended treatment and prevention of VTE versus placebo, and versus warfarin in the case of dabigatran. Compared with placebo treatment, each NOAC showed superior efficacy together with an acceptable safety profile during extended treatment periods of 6-18months. Patients receiving long-term NOAC therapy will still require regular risk factor assessment, but these agents may permit longer treatment duration with an improved benefit-risk profile. PMID:27263046

  7. Symptomatic Patients with Intraluminal Carotid Thrombus: Outcome with a Strategy of Initial Anticoagulation

    PubMed Central

    Vellimana, Ananth K.; Kadkhodayan, Yasha; Rich, Keith M.; Cross, Dewitte T.; Moran, Christopher J.; Zazulia, Allyson R.; Lee, Jin-Moo; Chicoine, Michael R.; Dacey, Ralph G.; Derdeyn, Colin P.; Zipfel, Gregory J.

    2013-01-01

    Background Optimal treatment for patients with symptomatic intraluminal carotid thrombus (ICT) remains poorly defined. Methods We performed a retrospective chart review of patients presenting to our institution between 2001 and 2011 with symptomatic ICT. Results Twenty-four patients (16 males, 8 females) with ICT presented with ischemic stroke (n=18) or TIA (n=6). All were treated initially with anticoagulation ± antiplatelet drugs. Eight of these patients had no or mild carotid stenosis on initial angiography and were treated with medical management alone. The remaining 16 patients had moderate or severe carotid stenosis on initial angiography. Of these, 10 underwent delayed revascularization (endarterectomy, n=8; angioplasty and stenting, n=2), 2 refused revascularization, and 4 were treated with medical therapy alone. One patient had multiple TIAs despite medical therapy and eventually underwent CEA; the remaining 23 patients had no TIAs. No patient suffered ischemic or hemorrhagic stroke while on anticoagulation, during the perioperative period or in long-term follow up; one patient died of an unrelated condition (mean follow-up = 16.4 months). Conclusion Our results suggest that initial anticoagulation of symptomatic ICT results in a low rate of recurrent ischemic events and that carotid revascularization, if indicated, can be safely performed in a delayed manner. PMID:23061393

  8. Plasma superwarfarin levels and vitamin K1 treatment in dogs with anticoagulant rodenticide poisoning.

    PubMed

    Robben, J H; Kuijpers, E A; Mout, H C

    1998-01-01

    The plasma concentration, plasma half-life (t1/2), and mean residence time (MRT) of rodenticide anticoagulants were determined in 21 dogs in which a preliminary diagnosis of anticoagulant rodenticide poisoning had been made. Brodifacoum, difethialone, and difenacoum were detected by high-performance liquid chromatography (HPLC) in the plasma of 13, 3, and 2 dogs, respectively. At presentation the plasma concentration ranged from below the detection limit (10 ng/L) to 851 ng/L. Toxin could not be detected in 3 dogs, despite these animals showing characteristic coagulation disturbances and a positive response to therapy with vitamin K1. In 7 dogs the estimated t1/2 of brodifacoum ranged from 0.9 to 4.7 (median 2.4) days with a MRT of 1.9 to 3.7 (median 2.8) days. In 2 dogs the individual t1/2 of difethialone was 2.2 and 3.2 days and the MRT was 2.3 and 2.8 days, respectively. Two dogs died during emergency treatment. Treatment in the remaining 19 dogs consisted of the administration of vitamin K1 and supportive therapy. The dose of vitamin K1 was reduced in a stepwise manner as long as the prothrombin time remained within physiological limits. The variation in initial plasma concentrations of the anticoagulants combined with the results of treatment support the idea that an individual therapeutic approach is warranted. PMID:9477532

  9. Safety and Efficacy Outcomes of Home and Hospital Warfarin Management Within a Pediatric Anticoagulation Clinic.

    PubMed

    Jones, Sophie; McLoughlin, Siobhan; Piovesan, Dana; Savoia, Helen; Monagle, Paul; Newall, Fiona

    2016-04-01

    The complexity of managing children with chronic disease has led to an increase in the use of long-term warfarin therapy. Time in therapeutic range (TTR) is the preferred method for determining efficacy and stability of warfarin management. This study aimed to determine the TTR achievement and incidence of adverse events among pediatric warfarin patients managed by an anticoagulation clinic over 12 months and to compare TTR achievement between patients self-testing (PST) at home and those monitored using routine methods. International normalized ratio (INR) results reported for 2012 for children currently having their warfarin therapy managed by a dedicated pediatric anticoagulation clinic were analyzed. Warfarin-related adverse events were recorded. A total of 164 patients were included. In total, 93 children performed PST and 71 children tested their INR at a hospital or pathology service. TTR achievement for the cohort was 67.1% (95% confidence interval, 64.4-69.7). A total of 69.2% of INR tests conducted at home were within the TTR compared with 64.3% of INR tests conducted at a hospital or pathology service (P=0.07). One major bleeding event occurred and there was 1 thrombotic episode. PST demonstrated noninferior warfarin stability compared with routine methods. Routine outcome evaluation of pediatric anticoagulation management within single institutions is necessary to confirm the success of such programs. PMID:26808370

  10. Anticoagulation and population risk of stroke and death in incident atrial fibrillation: a population-based cohort study

    PubMed Central

    Yu, Amy Y.X.; Malo, Shaun; Wilton, Stephen; Parkash, Ratika; Svenson, Lawrence W.; Hill, Michael D.

    2016-01-01

    Background: Atrial fibrillation increases the risk of stroke and death. Anticoagulation therapy is an effective treatment for stroke prevention, but remains underused in the community. We sought to determine the effectiveness and safety of anticoagulation therapy in an inception cohort with new-onset atrial fibrillation in the province of Alberta, Canada. Methods: We conducted a population-based cohort study of atrial fibrillation using an administrative database from Alberta's publicly funded and universally available health care system. All new-onset atrial fibrillation patients from Jan. 1, 2009, to Dec. 31, 2010, were included in the cohort and followed through Dec. 31, 2013. We assessed anticoagulation status as a predictor of stroke and death using time-to-event analysis and adjusted for sex and CHADS2 (congestive heart failure, hypertension, age ≥ 75 yr, diabetes mellitus and prior stroke or transient ischemic attack) score using Cox proportional hazards modelling. Results: We identified 10 745 patients, 7358 (68.5%) of whom received anticoagulation therapy, principally with warfarin (n = 6997, 95.1%). Anticoagulation therapy was associated with significantly decreased risk of ischemic stroke (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.58-0.82), all stroke (HR 0.77, 95% CI 0.65-0.91), all stroke and death (HR 0.70, 95% CI 0.62-0.72) and all-cause mortality (HR 0.67, 95% CI 0.62-0.72), despite an association with increased risk of hemorrhagic stroke (HR 1.92, 95% CI 1.17-3.16). There was a neutral association with subdural (HR 1.01, 95% CI 0.53-1.93) and gastrointestinal (HR 0.96, 95% CI 0.70-1.31) hemorrhage. Interpretation: Anticoagulation therapy is effective and safe for stroke prevention and decreases mortality in patients with incident atrial fibrillation. These population data support an aggressive approach to screening for atrial fibrillation and treatment with anticoagulant medicines to prevent stroke and death. PMID:27280108

  11. Severe Extra-Cerebral Anticoagulant-Related Bleeding in Intensive Care Unit: A Retrospective Study From 2000 to 2013.

    PubMed

    Hauguel, M; Boelle, Py; Pichereau, C; Bourcier, S; Bigé, N; Baudel, J L; Maury, E; Guidet, B; Ait-Oufella, H

    2015-11-01

    Bleeding is the most frequent complication of anticoagulant therapy, responsible for a number of hospitalizations or deaths. However, studies describing the management and prognosis factors of extra-cerebral anticoagulant-related bleedings in intensive care unit (ICU) are lacking.Retrospective observational study in an 18-bed ICU in a tertiary teaching hospital. From January 2000 to December 2013, all consecutive patients, older than 18 years, admitted for severe anticoagulant-related bleeding (SAB) except intracerebral site were included.A total of 100 patients were included, the mean age was 77 ± 11 years and 62% were women. SAB incidence in ICU doubled over 10 years (P = 0.03). In ICU, the average length of stay was 5 ± 6 days and mortality was 30%. Nonsurviving patients had a higher SAPS II (78 ± 24 vs 53 ± 24, P < 0.0001), a higher SOFA (9.0 ± 3.6 vs 4.7 ± 3.4, P < 0.0001) and received more frequently support therapy such as mechanical ventilation (87% vs 16%, P < 0.0001) and vasopressors (90% vs 27%, P < 0.0001). The volume of blood-derived products transfused was more important in nonsurvivors mainly during the first 24 hours of resuscitation. Rapid anticoagulant reversal therapy was associated with better prognosis (ICU survivors 66% vs 39%, Fisher test P = 0.04). Anterior abdominal wall was identified as a frequent site of bleeding (22%) due to epigastric artery injury during subcutaneous injection of heparin and was associated with a large mortality (55%).Extra-cerebral SAB is a life-threatening complication that requires rapid resuscitation and anticoagulant reversal therapy. Injection of heparin should be done carefully in the subcutaneous tissue thereby avoiding artery injury. PMID:26632750

  12. Should we test the prothrombin time in anticoagulated epistaxis patients?

    PubMed

    Soyka, Michael B; Holzmann, David

    2013-01-01

    Epistaxis is one of the most frequent emergencies in rhinology. Patients using anticoagulative medication are at increased risk for epistaxis. We evaluated the prothrombin time and the international normalized ratio (INR) in anticoagulated epistaxis patients. Patients suffering from epistaxis were prospectively included in a database and results from prothrombin testing were analyzed in the context of anticoagulation. One hundred sixteen of 591 epistaxis cases were identified to be on oral anticoagulation. The INR was found to be above therapeutic levels in 19 (16%) of these cases. We strongly recommend prothrombin time and INR testing in all epistaxis patients taking any sort of vitamin K antagonists. PMID:23772329

  13. Laboratory Measurement of the Anticoagulant Activity of the Target-specific Oral Anticoagulant Agents: A Systematic Review

    PubMed Central

    Cuker, Adam; Siegal, Deborah M.; Crowther, Mark A.; Garcia, David A.

    2014-01-01

    Background The target-specific oral anticoagulant agents (TSOACs) do not require routine laboratory monitoring. However, laboratory measurement may be desirable in special situations and populations. Objectives This study’s objective is to systematically review and summarize current evidence regarding laboratory measurement of the anticoagulant activity of dabigatran, rivaroxaban, and apixaban. Methods We searched PubMed and Web of Science for studies that reported a relationship between drug levels of dabigatran, rivaroxaban, and apixaban and coagulation assay results. Study quality was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Results We identified 17 eligible studies for dabigatran, 15 for rivaroxaban, and 4 for apixaban. For dabigatran, a normal thrombin time excludes clinically relevant drug concentrations. The activated partial thromboplastin time (APTT) and prothrombin time (PT) are less sensitive and may be normal at trough drug levels. The dilute thrombin time (R2 0.92–0.99) and ecarin-based assays (R2 0.92–1.00) show excellent linearity across on-therapy drug concentrations and may be used for drug quantification. In terms of rivaroxaban and apixaban, anti-Xa activity is linear (R2 0.89–1.00) over a wide range of drug levels and may be used for drug quantification. Undetectable anti-Xa activity likely excludes clinically relevant drug concentrations. The PT is less sensitive (especially for apixaban); a normal PT may not exclude clinically relevant levels. The APTT demonstrates insufficient sensitivity and linearity for quantification. Conclusions Dabigatran, rivaroxaban, and apixaban exhibit variable effects on coagulation assays. Understanding these effects facilitates interpretation of test results in TSOAC-treated patients. More information on the relationship between drug levels and clinical outcomes is needed. PMID:25212648

  14. Concept of a point of care test to detect new oral anticoagulants in urine samples

    PubMed Central

    2013-01-01

    New oral anticoagulants (NOAC) are approved for several indications for prophylaxis and treatment of venous thromboembolism and for prevention of embolism in atrial fibrillation at fixed daily doses without need of laboratory guided dose adjustment. Due to their low molecular weight of about 500 to 600 Dalton and their hydrophilicity free anticoagulant is excreted immediately through glomerular filtration into the urine. Impairment of renal function may increase the plasma concentration of the anticoagulants and lowered creatinine clearance is a declared contraindication. In contrast to the initial aim of development the anticoagulant effect is required to be determined in special clinical situations. Several specific and non-specific assays using plasma samples are currently undergoing standardization. As all NOACs are excreted into the urine, specific assays were developed for this matrix to determine them quantitatively of qualitatively. Urine samples can be easily and repetitively obtained avoiding problems and risks associated with blood sampling. The qualitative assay can be performed as a point of care test (POC) also by the patient by judging the different colours for the absence or presence of the drugs with the naked eye. The test is rapid (results available within 15 min), sensitive, specific and accurate and does not require a purified NOAC as control. The tests may be a tool for clinicians who need to know for treatment decisions if a NOAC is on board or not. As the tests are specific for oral direct thrombin inhibitors and for oral direct factor Xa inhibitors, the indication does not interfere with other qualitative POC test in development using clotting systems. The test may be indicated for patients at acute hospitalization, before surgery or central nervous system puncture anaesthesia, if fibrinolytic therapy is indicated, acute deterioration of renal function, and for control of adherence to therapy. PMID:23915217

  15. Cost of vitamin K antagonist anticoagulant treatment in patients with metallic prosthetic valve in mitral position

    PubMed Central

    Ene, Gabriela; Garcia Raso, Aránzazu; Gonzalez-Dominguez Weber, Almudena; Hidalgo-Vega, Álvaro; Llamas, Pilar

    2016-01-01

    Background: The initiation of oral anticoagulation therapy after valve replacement surgery requires strict monitoring because these patients are at high risk for the development of thrombotic complications and present an increased risk of bleeding. Objectives: The aim of this study was to examine the total healthcare costs of oral anticoagulant treatment with vitamin K antagonists in patients with metallic prosthetic valves in the mitral position. Methods: Data from clinical records were used in the study including international normalized ratio results, number of medical visits, type of anticoagulant, use of rescue medication and hospital admissions from related complications. The drug cost was calculated based on the official Spanish Ministry of Health price list. Monitoring expenses were included in the cost of the medical supplies used in the procedures. Hospitalization costs were calculated using the diagnosis-related group price for each case. Results: We collected data from 151 patients receiving oral anticoagulation therapy with vitamin K antagonist who were diagnosed with mitral prosthesis (n = 90), mitro-aortic prosthesis (n = 57), and mitral and tricuspid prosthesis (n = 4). The total direct healthcare cost was €15302.59, with a mean total cost per patient per year of €1558.15 (±2774.58) consisting of 44.38 (±42.30) for drug cost, €71.41 (±21.43) for international normalized ratio monitoring, €429.52 (±126.87) for medical visits, €26.31 (±28.38) for rescue medication and €986.53 (±2735.68) for related complications. Conclusion: Most direct healthcare costs associated with the sampled patients arose from the specialist-care monitoring required for treatment. Good monitoring is inversely related to direct healthcare costs. PMID:27579168

  16. Balancing ischaemia and bleeding risks with novel oral anticoagulants.

    PubMed

    Baber, Usman; Mastoris, Ioannis; Mehran, Roxana

    2014-12-01

    Vitamin K antagonists (VKAs) have long been the standard of care for treatment of venous thromboembolism (VTE), and thromboprophylaxis in atrial fibrillation (AF). Despite their efficacy, their use requires frequent monitoring and is complicated by drug-drug interactions and the need to maintain a narrow therapeutic window. Since 2009, novel oral anticoagulants (NOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, have become alternative options to VKAs owing to their predictable and safe pharmacological profiles. The overall clinical effect of these drugs, which is a balance between ischaemic benefit and bleeding harm, varies according to the clinical scenario. As adjunctive therapy to dual antiplatelet therapy in patients with acute coronary syndrome, NOACs are associated with incremental bleeding risks and modest benefits. For treatment of VTE, NOACs have a safer profile than VKAs and a similar efficacy. In thromboprophylaxis in AF, NOACs are associated with the greatest benefits by reducing both ischaemic events and haemorrhagic complications and might reduce mortality compared with VKAs. The role of NOACs continues to evolve as these drugs are evaluated in different patient populations, including those with renal impairment or with AF and undergoing percutaneous coronary intervention. PMID:25367652

  17. The Role of Anticoagulation Clinics in the Era of New Oral Anticoagulants

    PubMed Central

    Testa, Sophie; Paoletti, Oriana; Zimmermann, Anke; Bassi, Laura; Zambelli, Silvia; Cancellieri, Emilia

    2012-01-01

    Anticoagulation Clinics (ACs) are services specialized in management of patients on anticoagulant treatment. At present, ACs manage patients chiefly on antivitamin K antagonists (AVKs), but patient population has already changed in the last few years, because of an increase of treatments with other anticoagulant drugs, which require different management systems. The strong increase in the number of patients at AC, mainly on long-term treatment, has determined the development of web management, through telemedicine systems, improving the quality of life and maintaining the same clinical quality levels. New oral anticoagulants (NOAs) have shown to be as effective as AVK antagonists in stroke prevention in atrial fibrillation and for treatment of venous thromboembolism in addition to VTE prophylaxis in orthopaedic surgery, when administered at a fixed dose, but patient adherence and compliance are crucial for good quality treatment. At present, lacking data from the real world, an oversimplification of treatment with NOAs could cause unjustified risks for patients and also a possible future underuse of good drugs. For these reasons the vigilance must be high and ACs can have a crucial role in defining which is the best management for NOA patients and how to do it, as it happened for AVKs. PMID:23097696

  18. Bleeding Risk Index in an Anticoagulation Clinic

    PubMed Central

    Aspinall, Sherrie L; DeSanzo, Beth E; Trilli, Lauren E; Good, Chester B

    2005-01-01

    BACKGROUND The Outpatient Bleeding Risk Index (BRI) prospectively classified patients who were at high, intermediate, or low risk for warfarin-related major bleeding. However, there are only 2 published validation studies of the index and neither included veterans. OBJECTIVE To determine the accuracy of the BRI in patients attending a Veterans Affairs (VA) anticoagulation clinic and to specifically evaluate the accuracy of the BRI in patients with atrial fibrillation. DESIGN Retrospective cohort study. PATIENTS AND MEASUREMENTS Using the BRI, all patients managed by the Anticoagulation Clinic between January 1, 2001 and December 31, 2002 were classified as high, intermediate, or low risk for major bleeding. Bleeds were identified via quality-assurance reports. Poisson regression was used to determine whether there was an association between the index and the development of bleeding. RESULTS The rate of major bleeding was 10.6%, 2.5%, and 0.8% per patient-year of warfarin in the high-, intermediate-, and low-risk groups, respectively. Patients in the high-risk category had 14 times the rate of major bleeding of those in the low-risk group (incidence rate ratio (IRR) 14; 95% confidence interval (CI), 1.9 to 104.7). The rate of major bleeding was significantly different between the high- and intermediate-risk categories (P<.001). Among those with atrial fibrillation, patients in the high-risk category had 6 times the major bleeding rate of those in the intermediate- and low-risk groups combined (IRR=6; 95% CI, 2.4 to 15.3). CONCLUSIONS The BRI discriminates between high- and intermediate-risk patients in a VA anticoagulation clinic, including those with atrial fibrillation. PMID:16307625

  19. Comparison of the haemostatic properties of conventional monopolar and bipolar transurethral resection of the prostate in patients on oral anticoagulants

    PubMed Central

    Michielsen, Dirk P.J.; Coomans, Danny; Van Lersberghe, Caroline; Braeckman, Johan G.

    2011-01-01

    Introduction The aim of study is comparing the haemostatic properties of conventional monopolar resection (TURP) and bipolar transurethral resection in saline (TURIS) of the prostate in patients under chronic oral anticoagulants. Material and methods Out of a cohort group of 550 endoscopic resections for bladder outlet obstruction, 176 patients on chronic oral anticoagulant therapy required endoscopic resection either by monopolar TURP or bipolar TURIS technology. Changes in haemoglobin, blood transfusion, and clot retention were compared between both groups. Results Mean postoperative change in haemoglobin level was –1.21 ±0.92 mg/dl in the TURP group compared to –1.29 ±0.99 mg/dl in the TURIS group (p = 0.603). The need for blood transfusions and the mean numbers of units transfused did not significantly differ between the 2 groups. Clot retention appeared in 12 patients (15%) in the TURP group compared to 13 patients (13%) in the TURIS group (p = 0.828). Conclusions Despite promising experimental results of better haemostasis and deeper coagulation depth, bipolar technology does not permit one to reduce the amount of blood loss when compared to patients treated by conventional monopolar technology in this study group of patients on oral anticoagulation therapy. Patients on oral anticoagulants suffer more incidents of clot retention, which sometimes results in re-hospitalisation. PMID:22291832

  20. Anticoagulant activity of original synthetic peptide derivatives.

    PubMed

    Drozd, N N; Tolstenkov, A S; Makarov, V A; Miphtakhova, N T; Voyushina, T L; Sergeev, M E

    2008-01-01

    Original synthetic peptide derivatives exhibit anticoagulant activity in vitro and in vivo. They delayed fibrin clot formation from human blood plasma in tests for the intrinsic coagulation pathway (activated partial thromboplastin time) and final stage of plasma coagulation (thrombin time) and inhibited amidolytic activity of thrombin. We determined the minimum effective dose of the most active compound providing a 2-fold lengthening of blood clotting time (activated partial thromboplastin time test and thrombin time test), which persisted for 2-3 h. PMID:19024001

  1. Shortfalls using second-generation anticoagulant rodenticides.

    PubMed

    Borst, G H A; Counotte, G H M

    2002-03-01

    Second-generation anticoagulant rodenticides can give rise to unexpected casualties in nontarget species in zoos. The first two offspring of a pair of turkey vultures (Cathartes aura) died of brodifacoum toxicosis. The adult birds fed rodenticide-killed mice to their offspring. There are previous case reports of small carnivorous birds (Dacelo novae-guinae and Tockus deckeni) killed eating poisoned (difenacoum and brodifacoum) mice. Even a granivorous species (Rollulus roulroul) died, probably by contamination of its food by cockroaches that transported the rodenticide. PMID:12216801

  2. Anticoagulants: Major Advances Without Clear Consensus.

    PubMed

    Hohl, R J

    2016-08-01

    Therapeutics for thrombosis were discovered because of observations made nearly one hundred years ago. The mainstays of these treatments have been either heparin or warfarin, with the latter being preferred for long-term anticoagulation. In the last six years, newer agents with antigoagulant activities have been approved for clinical use. These agents have advantages and disadvantages over warfarin and consensus for their use is still being formed, as is the manner in which the more traditional agents, such as warfarin, should be used and monitored. PMID:27393187

  3. New anticoagulants: pharmacology and clinical studies.

    PubMed

    Samama, Charles Marc

    2011-02-01

    The marketing of new anticoagulant drugs has led us to review the development of rivaroxaban and apixaban (oral anti-Xa drugs) and dabigatran (an oral thrombin inhibitor). The results are different in terms of efficacy and tolerance. Each molecule has its own field of application but it is not at all certain that each will find its place. Though the results are favourable for these orally active drugs in the orthopaedic setting, it is clear that only cardiological applications will give a final green light for these products. The future will be fascinating in this regard. PMID:21404139

  4. Emergency reversal of anticoagulation with a three-factor prothrombin complex concentrate in patients with intracranial haemorrhage

    PubMed Central

    Imberti, Davide; Barillari, Giovanni; Biasioli, Chiara; Bianchi, Marina; Contino, Laura; Duce, Rita; D’Incà, Marco; Gnani, Maria Cristina; Mari, Elisa; Ageno, Walter

    2011-01-01

    Background Intracranial haemorrhage is a serious and potentially fatal complication of oral anticoagulant therapy. Prothrombin complex concentrates can substantially shorten the time needed to reverse the effects of oral anticoagulants. The aim of this study was to determine the efficacy and safety of a prothrombin complex concentrate for rapid reversal of oral anticoagulant therapy in patients with intracranial haemorrhage. Methods Patients receiving oral anticoagulant therapy and suffering from acute intracranial haemorrhage were eligible for this prospective cohort study if their International Normalised Ratio (INR) was higher than or equal to 2.0. The prothrombin complex concentrate was infused at doses of 35–50 IU/kg, stratified according to the initial INR. Results Forty-six patients (25 males; mean age: 75 years; range 38–92 years) were enrolled. The median INR at presentation was 3.5 (range, 2–9). At 30 minutes after administration of the prothrombin complex concentrate, the median INR was 1.3 (range, 0.9–3), and the INR then declined to less than or equal to 1.5 in 75% of patients. The benefit of the prothrombin complex concentrate was maintained for a long time, since the median INR remained lower than or equal to 1.5 (median, 1.16; range, 0.9–2.2) at 96% of all post-infusion time-points up to 96 hours. No thrombotic complications or significant adverse events were observed during hospitalisation; six patients (13%) died, but none of these deaths was judged to be related to administration of the prothrombin complex concentrate. Conclusions Prothrombin complex concentrates are an effective, rapid and safe treatment for the urgent reversal of oral anticoagulation in patients with intracranial haemorrhage. Broader use of prothrombin complex concentrates in this clinical setting appears to be appropriate. PMID:21251465

  5. Real-world characteristics of hospitalized frail elderly patients with atrial fibrillation: can we improve the current prescription of anticoagulants?

    PubMed Central

    Annoni, Giorgio; Mazzola, Paolo

    2016-01-01

    Background In elderly patients, especially those older than 80 years, atrial fibrillation (AF) is associated with an almost 25% increased risk of stroke. Stroke prophylaxis with anticoagulants is therefore highly recommended. The prevalence of factors that have been associated with a lower rate of prescription and adherence to anticoagulant therapy in these patients is little known. The objective of this study was to explore the clinical characteristics of elderly subjects, with and without AF, consecutively admitted to an acute geriatric unit, discussing factors that may decrease the persistence on stroke prophylaxis therapy. We also highlight possible strategies to overcome the barriers conditioning the current underuse of oral anticoagulants in this segment of the population. Methods A retrospective observational study was performed on a cohort of elderly patients with and without AF admitted to the Acute Geriatric Unit of San Gerardo Hospital (Monza, Italy). Results Compared to patients without AF (n = 1216), those with AF (n = 403) had a higher Charlson Comorbidity Index (3 vs. 2, P < 0.001), number of administered drugs (4 vs. 3, P < 0.001), rate of heart failure (36.5% vs. 12%, P < 0.001) and chronic kidney disease (20.6 vs. 13.2, P < 0.001). Many patients with AF were frail (54%) or pre-frail (29%). Conclusions Elderly patients with AF have higher rates of conditions that affect adherence to traditional anticoagulant therapy (vitamin K antagonists, VKA). New direct oral anticoagulants (DOAs) can help overcome this problem. In order to prescribe the most appropriate VKA or DOAs, with the best efficacy/safety profile and the highest compliance, a comprehensive geriatric assessment should always accompany the scores for thrombotic and hemorrhagic risk stratification. PMID:27103917

  6. Avoiding Medication Errors: Reducing Harm in Residents Using Oral Anticoagulants.

    PubMed

    Grissinger, Matthew; Gaunt, Michael J; Rich, Darryl S

    2016-01-01

    Medication errors involving oral anticoagulants have led to serious adverse events, including hemorrhage, treatment failures leading to thromboembolic events, and death. This article will highlight medication errors that may arise during the use of oral anticoagulants and provide risk-reduction strategies to address the potential for error and patient harm. PMID:27250070

  7. Intracranial hemorrhage in cancer patients treated with anticoagulation.

    PubMed

    Weinstock, Matthew J; Uhlmann, Erik J; Zwicker, Jeffrey I

    2016-04-01

    Both venous thromboembolism and intracranial metastases are common complications in the setting of primary brain tumors and metastatic malignancies. Anticoagulation is indicated in the presence of cancer-associated thrombosis in order to limit the risk of pulmonary embolism; however, there is reluctance to initiate anticoagulation in the setting of intracranial metastatic disease due to potential for intracranial hemorrhage. Recent evidence suggests that therapeutic anticoagulation can be safely administered in the setting of metastatic brain tumors. This review examines the current understanding of the pathophysiology of intracranial hemorrhage in malignancy, describes the incidence of intracranial hemorrhage in the setting of brain tumors with therapeutic anticoagulation, and outlines management strategies relevant to the treatment of intracranial hemorrhage in the setting of anticoagulation. PMID:27067980

  8. New oral anticoagulants – a practical guide

    PubMed Central

    Ciurus, Tomasz; Sobczak, Sebastian; Cichocka-Radwan, Anna

    2015-01-01

    Oral direct inhibitors of thrombin and activated factor Xa are approved as new anticoagulant drugs. In contrast to vitamin K antagonists (VKA) and heparins, the new agents have single targets in the coagulation cascade and more predictable pharmacokinetics, but they lack validated and available antidotes. Unlike VKA, they do not require routine monitoring of coagulation. However, the measurement of their pharmacologic effects might be of value in selected patients. They interfere with the routine coagulation tests, which should be interpreted with caution. Specific tests exist and can be used in case of emergencies. Adequate supportive care and temporary removal of all antithrombotic agents constitute the basis for management of serious bleeding complications. The administration of coagulation factors, such as fresh frozen plasma, prothrombin complex concentrates or recombinant activated FVII, can benefit in life-threatening bleeding or emergency surgery. Specific antidotes for non-vitamin K oral anticoagulants are in clinical development. This review aims at answering in a brief and simplified manner some clinical questions. PMID:26336492

  9. The role of anticoagulation in the measurement of platelet volumes.

    PubMed

    Thompson, C B; Diaz, D D; Quinn, P G; Lapins, M; Kurtz, S R; Valeri, C R

    1983-09-01

    The effect of anticoagulation on platelet size stability was studied using blood collected in seven different anticoagulants and stored at room temperature for up to eight hours. The mean platelet volume (MPV) value was most stable in blood collected in 15% ACD and ACD/Na2EDTA. In blood collected in Na2EDTA, K3EDTA, or 11.9% ACD, there was an increase in MPV in the first two hours, after which the MPVs remained stable up to eight hours. Sodium citrate and heparin proved unreliable for the measurement of platelet volume. Platelet counts were stable (less than 5% variation) in all anticoagulants except heparin, which had 16% variation for the eight hours of study. Simultaneously, RBC counts and mean corpuscular volume (MCV) measurements were stable in all seven anticoagulants, with sodium citrate producing the most variation. A negative correlation was observed between MCV and pH of the anticoagulated blood. WBC counts showed less than 3% variation in all anticoagulants except sodium citrate and heparin. Separate experiments demonstrated that electrolyte composition, pH, tonicity, and method of calcium chelation all influenced the stability of the MPV. Of the anticoagulants studied, ACD/Na2 EDTA appeared to provide the best conditions of anticoagulation for both routine clinical and research laboratory measurement of the MPV. It inhibited platelet activation but left the platelets in their normal discoid shape. Platelets could be removed from the anticoagulant and studied in functional assays for up to eight hours after blood drawing. Both platelet counts and MPVs remained stable in blood collected in ACD/Na2 EDTA anticoagulant for up to eight hours at room temperature. In 52 volunteers studied, an inverse correlation (r = -0.72, P less than 0.001) was observed between platelet count and MPV, suggesting that the circulating platelet mass may be a more important indicator of platelet homeostasis than either the platelet count or the mean platelet volume alone. PMID

  10. Brave new world: the current and future use of novel anticoagulants.

    PubMed

    Spyropoulos, Alex C

    2008-01-01

    Advances in antithrombotic therapy began when traditional anticoagulant agents such as heparin and the vitamin K antagonists like Coumadin became commercially available in the 1940s and 1950s. Inherent limitations of these compounds, including the need for monitoring and multiple food and drug interactions (with coumadin), spurred the development of newer parenteral compounds like low molecular weight heparin, the pentasaccharide fondaparinux, and direct thrombin inhibitors such as hirudin, argatroban and bivalirudin with advantages over traditional compounds. Despite the failure of the first oral anticoagulant in 50 years--the direct thrombin inhibitor ximelagatran--due to issues with liver toxicity, new oral agents such as the Factor Xa inhibitors rivaroxaban, apixaban, YM-150, and DU-176b and oral direct thrombin inhibitors such as dabigatran are in advanced stages of development, with dabigatran and rivaroxaban now approved for use outside of the United States for thromboprophylaxis in the setting of orthopedic surgery. These and other novel agents have the potential to greatly expand our armamentarium to treat thromboembolic disease, with more targeted approaches to specific procoagulant complexes, a predictable anticoagulant response that does not require monitoring, and use in both acute and long-term treatment settings. PMID:18835010

  11. Evolving use of new oral anticoagulants for treatment of venous thromboembolism

    PubMed Central

    Yeh, Calvin H.; Gross, Peter L.

    2014-01-01

    The new oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban, and edoxaban, are poised to replace warfarin for treatment of the majority of patients with venous thromboembolism (VTE). With a rapid onset of action and the capacity to be administered in fixed doses without routine coagulation monitoring, NOACs streamline VTE treatment. In phase 3 trials in patients with acute symptomatic VTE, NOACs have been shown to be noninferior to conventional anticoagulant therapy for prevention of recurrence and are associated with less bleeding. Rivaroxaban and dabigatran are already licensed for VTE treatment in the United States, and apixaban and edoxaban are under regulatory consideration for this indication. As the number of approved drugs increases, clinicians will need to choose the right anticoagulant for the right VTE patient. To help with this decision, this review (1) compares the pharmacologic profiles of the NOACs, (2) outlines the unique design features of the phase 3 trials that evaluated the NOACs for VTE treatment, (3) reviews the results of these trials highlighting similarities and differences in the findings, (4) provides perspective about which VTE patients should receive conventional treatment or are candidates for NOACs, and (5) offers suggestions about how to choose among the NOACs. PMID:24923298

  12. Translational insights into traumatic brain injury occurring during dabigatran or warfarin anticoagulation

    PubMed Central

    Schaefer, Jan Hendrik; Leung, Wendy; Wu, Limin; Van Cott, Elizabeth M; Lok, Josephine; Whalen, Michael; van Leyen, Klaus; Lauer, Arne; van Ryn, Joanne; Lo, Eng H; Foerch, Christian

    2014-01-01

    To date, only limited data are available on the effects of pretreatment with novel oral anticoagulants in the event of traumatic brain injury (TBI). We determined intracerebral hemorrhage volume and functional outcome in a standardized TBI model in mice treated with warfarin or dabigatran. Additionally, we investigated whether excess concentrations of dabigatran could increase bleeding and whether this was preventable by using prothrombin complex concentrate (PCC). C57 mice were treated orally with warfarin or dabigatran; sham-treated mice served as controls. Effective anticoagulation was verified by measurement of international normalized ratio and diluted thrombin time, and TBI was induced by controlled cortical impact (CCI). Twenty-four hours after CCI, intracerebral hemorrhage volume was larger in warfarin-pretreated mice than in controls (10.1±4.9 vs 4.1±1.7 μL; analysis of variance post hoc P=0.001), but no difference was found between controls and dabigatran-pretreated mice (5.3±1.5 μL). PCC applied 30 minutes after CCI did not reliably reduce intracerebral hemorrhage induced by excess dabigatran concentration compared with saline (10.4±11.2 vs 8.7±7.1 μL). Our data suggest pathophysiological differences in TBI occurring during warfarin and dabigatran anticoagulation. The reduced hemorrhage formation under dabigatran therapy could present a safety advantage compared with warfarin. An excess dabigatran concentration, however, can increase hemorrhage. PMID:24549187

  13. Prescribing patterns of target-specific oral anticoagulants: an academic hospital perspective

    PubMed Central

    Johnson, Stacy A.; Yarbrough, Peter M.; Rose, Richard S.; Lanspa, Michael J.

    2015-01-01

    Target-specific oral anticoagulants have been rapidly adopted into clinical practice for stroke prophylaxis and venous thromboembolism treatment, raising concerns about off-label prescribing practices. We conducted a retrospective review of consecutive patients prescribed dabigatran, rivaroxaban or apixaban prior to inpatient hospitalization over an 18-month period to examine the off-label prescribing frequency, contraindications and related complications. Chart review included baseline demographics, hospital admitting service, outpatient prescribing service, renal function, therapeutic indication, echocardiographic findings, contraindications, major bleeding events and vital status. We identified 160 patients who received a target-specific oral anticoagulant prior to hospitalization. Over half (53.1%) of the patients received rivaroxaban, 43.7% received dabigatran and 3.1% received apixaban. Atrial fibrillation (68.1%) and venous thromboembolism treatment (25.6%) were the most common indications. Ninety percent of patients had a U.S. Foods and Drugs Administration (FDA)-approved indication for therapy. Major bleeding events occurred in 4.4% of patients. Cardiology was the most common prescribing and admitting service (43.8 and 31.3%), and more frequently adhered to FDA-approved indications (97 vs. 84%, P = 0.01). There were no significant differences between prescribing services regarding major contraindications (P = 0.14) and major bleeding events (P = 0.77). Off-label prescription rates for target-specific oral anticoagulants were infrequent and not associated with increased adverse events. PMID:26414695

  14. Oral anticoagulants in development: focus on thromboprophylaxis in patients undergoing orthopaedic surgery.

    PubMed

    Eriksson, Bengt I; Quinlan, Daniel J

    2006-01-01

    Current anticoagulant provision is dominated by parenteral heparin and oral warfarin, which act by inhibiting several steps of the coagulation pathway indirectly. Recent research efforts have focused on the identification of small molecule inhibitors of the coagulation enzymes as novel therapies for thrombotic disorders. There has been particular success in developing nonpeptidic, orally available, small molecules to directly inhibit the key proteases, factor IIa and factor Xa. Of the new oral anticoagulants in development, the two agents in the most advanced stage are dabigatran etexilate (BIBR 1048) and rivaroxaban (BAY 59-7939), which inhibit factor IIa and factor Xa, respectively. Other agents in the early stages of development include several Xa inhibitors (LY-517717, YM150, DU-176b and apixaban [BMS-562247]), a factor IXa inhibitor (TTP889), and an orally active glycosaminoglycan enhancer (odiparcil [SB-424323]), which indirectly enhances thrombin inhibition via heparin cofactor II. Results have been reported from important, phase II dose-finding studies, and a number of registration-track phase III studies have been initiated, reflecting the drive towards potentially more effective, but primarily safer and more convenient therapies for the prevention and treatment of venous and arterial thrombosis. Indeed, two unmet needs for anticoagulation that can be easily identified are safety and ease of use. Safety relates primarily to the incidence of major bleeding and this remains the key concern of orthopaedic surgeons, over and above any efficacy advantage, and convenience of use, which centres on oral administration replacing the need for injections. The clinical development of these new anticoagulants is following the well tested strategy of dose-ranging and registration studies in major orthopaedic surgery, prior to development in arterial indications. There are a number of subtle issues, including the timing of the first perioperative dose, duration of

  15. Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry

    PubMed Central

    Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M.; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph. Gabriel

    2015-01-01

    Background Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. Methods and Findings CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. Conclusions In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. Trial Registration ISRCTN registry of clinical trials: ISRCTN43070564. PMID:25915904

  16. [Acute and chronic anticoagulation therapy in relation to joint replacements].

    PubMed

    Malý, Jaroslav

    2015-06-01

    Thromboembolic disease (TED) is a considerable social and health problem. The solution evidently consists in the prevention of TED in clinical fields, not in the treatment itself. We can assume that effective prevention consequently reduces the cost of the following treatment. A lethal pulmonary embolism (PE) can be the first and the final clinical manifestation in patients with an asymptomatic deep venous thrombosis. This makes the systematic prevention of venous thromboembolism in higher risk patients necessary. Unfortunately, pharmacological prevention has been used less than would be needed. Inseparable from the TED prevention are physical methods. Pharmacological possibilities of the thromboembolic disease prevention were significantly extended within the past decade. To ensure the TED prevention after the total replacement (TEP) of hip and knee joints the following rules need to be observed: the TED prevention should be effected with LMWH, fondaparinux, dabigatran, rivaroxaban or apixaban for a period of 28-35 days after the hip joint replacement surgery and for 14 days after the knee joint replacement. The use of ASA, dextran and UFH as a thromboprophylaxis after the hip and knee joint TEP is not justified within the Czech Republic. Physical means (graduated compression stockings or IPC) can be used to support the recommended pharmacological treatment, they should not be used individually except in cases where pharmacological thromboprophylaxis is contraindicated.Key words: apixaban - dabigatran - LMWH - rivaroxaban - total hip and knee joint replacement - thromboembolic disease. PMID:26258975

  17. Anticoagulation Management in Patients with Pacemaker-Detected Atrial Fibrillation

    PubMed Central

    Poposka, Lidija; Boskov, Vladimir; Risteski, Dejan; Taleski, Jane; Georgievska-Ismail, Ljubica

    2016-01-01

    INTRODUCTION: In patients with an implanted pacemaker, asymptomatic atrial fibrillation (AF) is associated with an increased risk of thrombo-embolic complications. There is still no consensus which duration of episodes of atrial fibrillation should be taken as an indicator for inclusion of oral anticoagulation therapy (OAC). MATERIAL AND METHODS: A total of 104 patients who had no AF episodes in the past and have an indication for permanent pacing were included in the study. RESULTS: During an average follow-up of 18 months, 33 of the patients developed episodes of AF. Inclusion of OAC was performed in 17 patients, in whom AF was recorded, although in all patients CHA2DS2-VASc score was ≥ 1. The inclusion of OAC showed a statistically significant correlation with increasing duration of episodes of AF (r = 0.502, p = 0.003). During the follow-up period none of the patients developed thrombo-embolic complication. CONCLUSION: Considering that our group of patients had no thrombo-embolic events, we could conclude that dividing the AF episodes in less than 1% in 24 hours and longer than 1% within 24 hours could be an indicator for decision-making to include OAK if the CHA2DS2-VASc score is ≥ 1. PMID:27335594

  18. Thromboembolism and anticoagulation after Fontan surgery

    PubMed Central

    Viswanathan, Sangeetha

    2016-01-01

    This review attempts to answer the common questions faced by a clinician regarding thromboembolism and thromboprophylaxis in patients following Fontan surgery. The review is in an easy to understand question and answer format and discusses the currently available literature on the subject in an attempt to arrive at practical clinically relevant solutions. Patients who have undergone the Fontan operation are at a high risk for thromboembolism. Based on available evidence, there is a strong rationale for thromboprophylaxis. However, it is not clear as to which agent should be administered to prevent thromboembolic events. While the available evidence suggests that antiplatelet agents alone may be as good as oral anticoagulants, there is a need for a large multicenter randomized control trial comparing these two common strategies to deliver a clear verdict. PMID:27625521

  19. Thromboembolism and anticoagulation after Fontan surgery.

    PubMed

    Viswanathan, Sangeetha

    2016-01-01

    This review attempts to answer the common questions faced by a clinician regarding thromboembolism and thromboprophylaxis in patients following Fontan surgery. The review is in an easy to understand question and answer format and discusses the currently available literature on the subject in an attempt to arrive at practical clinically relevant solutions. Patients who have undergone the Fontan operation are at a high risk for thromboembolism. Based on available evidence, there is a strong rationale for thromboprophylaxis. However, it is not clear as to which agent should be administered to prevent thromboembolic events. While the available evidence suggests that antiplatelet agents alone may be as good as oral anticoagulants, there is a need for a large multicenter randomized control trial comparing these two common strategies to deliver a clear verdict. PMID:27625521

  20. Management Overview: Taking a Patient with Intracranial Hemorrhage Related to Direct Oral Anticoagulants to the Operating Room.

    PubMed

    Alturki, Abdulrahman; Alamri, Abdullah; Badawy, Mohamed; Teitelbaum, Jeanne

    2016-06-01

    Options for anticoagulation have been expanding constantly during the past few years, providing a greater number of agents for prevention and management of thromboembolic disease. Although heparins and vitamin K antagonists (VKAs) has been used extensively for many decades, their narrow therapeutic range, interactions with other medications and food, and the need for routine monitoring of blood levels have led to the search for less problematic alternatives. Direct oral anticoagulants represent an important advance in anticoagulation therapy, directly inhibiting thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) they represent an effective and safe alternatives to VKAs and heparins in the prevention and treatment of several thromboembolic disorders. DOCAs are associated with a low overall intracranial hemorrhage risk; however, life-threatening bleeding can occur. Reversal agents are approved for some and under development for others, concerns over the lack of antidotes or difficulty in obtaining them has tempered enthusiasm for their use because of the perception of better safety with heparins and VKAs as a result of the availability of effective reversal strategies. Appropriate use of these agents requires knowledge of their individual characteristics, mechanisms of action, pharmacokinetics, ways of monitoring, and when needed, manage patients in need of urgent surgery especially in life-threatening bleeds. This article provides a suggested comprehensive approach to manage patients with intracranial hemorrhage while on direct oral anticoagulants who require an urgent surgical intervention and who cannot wait for plasma concentration to decline. PMID:26960279

  1. Correlation between International Normalized Ratio values and sufficiency of two different local hemostatic measures in anticoagulated patients

    PubMed Central

    Amer, Mohamed Zaghlool; Mourad, Samah I.; Salem, Ahmed S.; Abdelfadil, Ehab

    2014-01-01

    Objectives: The management of patients receiving oral anticoagulant therapy (OAT) undergoing minor oral surgeries is controversial. This study was designed to evaluate the correlation between International Normalized Ratio (INR) values and the sufficiency of two different local hemostatic measures in controlling postextraction bleeding in anticoagulated patients. Materials and Methods: One hundred and sixty patients receiving Warfarin OAT were included in this study. Patients were selected so that 80 patients have INR values of ≤2, whereas the remaining patients have the INR values ranging from 2 to 3. Forty patients were then randomly selected from each category to form two equal groups. Forty-five patients who had never been on OAT were selected as a negative control group (group 1). Failure to achieve hemostasis using a pressure pack was managed using either tranexamic acid (group 2) or Ankaferd Blood Stopper (ABS) (group 3). Results: The INR values of patients included in group 2 and 3 ranged from 1.5 to 3, with a mean of 2.2. No significant difference was recorded between the use of either tranexamic acid or ABS in achieving hemostasis in anticoagulated patients with INR values ranging between 2 and 3 (P = 0.93). Conclusion: Based on our findings, ABS is a hemostatic agent of good efficacy. The effect of ABS in controlling post-extraction bleeding in anticoagulated patients with INR values ≤3 is comparable to tranexamic acid with no evidence to support the superiority of tranexamic acid over ABS. PMID:25512727

  2. The management of dental patients taking new generation oral anticoagulants.

    PubMed

    Scott, Alun; Gibson, John; Crighton, Alexander

    2014-11-01

    Recently, new oral anticoagulants have been introduced as alternatives to warfarin. While national guidelines for treatment of dental patients taking warfarin as an anticoagulant are well-established, no such information is available for these novel therapeutic agents. At present, the local guidance available is contradictory between different health boards/health planning units, and liaison with the medical practitioner managing the individual patient's anticoagulation is imperative if any invasive procedure is proposed. This paper examines the available evidence regarding these drugs and sets out proposals for clinical guidance of dental practitioners treating these patients in primary dental care. PMID:25668377

  3. Unplanned pregnancy on a direct oral anticoagulant (Rivaroxaban): A warning.

    PubMed

    Myers, B; Neal, R; Myers, O; Ruparelia, M

    2016-03-01

    Direct oral anticoagulants (DOACs or NOACs -non-vitamin K oral anticoagulants), as the name suggests, are oral anticoagulants with a direct inhibitory action either against factor X or factor II (thrombin). Pregnant women were excluded from participating in all the large trials of the DOACs and they are considered contra-indicated in pregnancy and breast feeding. We present a case of inadvertent exposure to rivaroxaban in a woman who presented at 25 weeks' gestation. The management of her pregnancy and delivery is described, and the previous published case reports are reviewed with a discussion about the use of DOACs in woman of childbearing age. PMID:27512489

  4. Synthetic oligosaccharides as heparin-mimetics displaying anticoagulant properties.

    PubMed

    Avci, Fikri Y; Karst, Nathalie A; Linhardt, Robert J

    2003-01-01

    Heparin and low molecular weight heparins are major clinical anticoagulants and the drugs of choice for the treatment of deep venous thrombosis. The discovery of an antithrombin binding domain in heparin focused interest on understanding the mechanism of heparin's antithrombotic/ anticoagulant activity. Various heparin-mimetic oligosaccharides have been prepared in an effort to replace polydisperse heparin and low molecular weight heparins with a structurally-defined anticoagulant. The goal of attaining a heparin-mimetic with no unwanted side-effects has also provided motivation for these efforts. This article reviews structure-activity relationship (SAR) of structurally-defined heparin-mimetic oligosaccharides. PMID:14529394

  5. [Duration of antivitamin K therapy in venous thromboembolic disease].

    PubMed

    Ferrari, E; Baudouy, M; Morand, P

    1995-12-01

    The necessity for anticoagulant treatment after pulmonary embolism or deep vein thrombosis has been demonstrated. The modalities of this treatment have been established, especially the value of initial heparin relayed by oral antivitamin K therapy with a target INR value between 2 and 3. The last question remaining in this protocol is that of the duration of anticoagulant treatment. The choice of duration of anticoagulation should take into consideration two potential complications: haemorrhage due to over-anticoagulation and excessive duration of therapy, and recurrent thromboembolism which could result from an inadequate duration of therapy. Several trials have addressed this question and have led to a consensus of opinion: therefore, secondary venous thrombo-embolic disease, occurring under known, special circumstances, the cause of which has been treated, should be given 4 to 6 weeks anticoagulant therapy. In the other cases, so-called idiopathic venous thromboembolism (the proportion of which is on the increase), recent studies are inadequate to reach a consensus. These "idiopathic" forms are characterised by a higher incidence of recurrent thromboembolism of "secondary" cancer and coagulation abnormalities. The search for the optimal duration of anticoagulant therapy in these forms requires prospective trials taking their features into account and should lead to further therapeutic options. The evaluation of longer treatment protocols with less intensive degrees of anticoagulation and of alternatives to oral vitamin K antagonists is justified. PMID:8729371

  6. Efficacy and Safety of Novel Anticoagulants Compared with Established Agents

    PubMed Central

    Rybak, Iwona; Ehle, Michael; Buckley, Leo; Fanikos, John

    2011-01-01

    Dabigatran, rivaroxaban, and apixaban are novel oral anticoagulants that offer major advantages over existing agents. The onset of the anticoagulant effect of these agents is rapid. Each agent has a predictable anticoagulant response that eliminates the need for monitoring. Clinical trials have been completed with all three agents in the prevention and treatment of the three leading causes of cardiovascular death: myocardial infarction, stroke, and venous thromboembolism (VTE). Novel agents have shown reduced or similar rates of thrombosis, major bleeding, and adverse events when weighed against either low molecular weight heparin or warfarin. Additional trials are underway and more agents are in development. As a result, novel anticoagulants may impact physician prescribing practices and warrant consideration in patients requiring thrombosis management. PMID:23556088

  7. Development and Validation of an Oral Anticoagulation Knowledge Tool (AKT)

    PubMed Central

    Obamiro, Kehinde O.; Chalmers, Leanne; Bereznicki, Luke R. E.

    2016-01-01

    Background Assessing and improving patients’ anticoagulation knowledge can lead to better treatment outcomes. While validated knowledge instruments exist for use in people taking warfarin, these tools are not necessarily applicable to patients taking direct-acting oral anticoagulants. Objective To develop and validate an oral anticoagulation knowledge instrument that is applicable to all oral anticoagulant medications. Methods Ten anticoagulation experts participated in the development of the Anticoagulation Knowledge Tool to ensure content validity. The knowledge instrument was administered to three groups of participants comprising of 44 pharmacists, 50 patients and 50 members of the general public. A subgroup of participants in the patient and pharmacist group were retested approximately 2–3 months after the initial testing. Statistical tests were conducted to determine the validity and reliability of the scale, and item analysis was used to determine the performance of individual questions. Results The 28-item instrument developed had a scale content validity index of 0.92, supporting content validity. The pharmacist group’s mean score was significantly higher than that of the patient group, and the patient group scored significantly higher than the general public group (94% vs 62% vs 20%, respectively; p<0.001), supporting construct validity. Internal consistency reliability was acceptable with a Cronbach’s α value of > 0.7 across the three groups, and the test–retest reliability was confirmed with a Pearson’s correlation coefficient of 0.72 and 0.78 for the pharmacist and patient groups, respectively. Conclusion The Anticoagulation Knowledge Tool is a valid and reliable instrument that can be used in routine clinical practice to assess patients’ anticoagulation knowledge. PMID:27351746

  8. Addressing Barriers to Optimal Oral Anticoagulation Use and Persistence Among Patients with Atrial Fibrillation: Proceedings, Washington, DC, December 3–4, 2012

    PubMed Central

    Hess, Paul L.; Mirro, Michael J.; Diener, Hans-Christoph; Eikelboom, John W.; Al-Khatib, Sana M.; Hylek, Elaine M.; Bosworth, Hayden B.; Gersh, Bernard J.; Singer, Daniel E.; Flaker, Greg; Mega, Jessica L.; Peterson, Eric D.; Rumsfeld, John S.; Steinberg, Benjamin A.; Kakkar, Ajay K.; Califf, Robert M.; Granger, Christopher B.

    2014-01-01

    Approximately half of patients with atrial fibrillation (AF) and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs); and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3–4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to develop and disseminate shared decision-making tools, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational datasets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives. PMID:25173533

  9. Long-Term Population-Based Cerebral Ischemic Event and Cognitive Outcomes of Direct Oral Anticoagulants Compared With Warfarin Among Long-term Anticoagulated Patients for Atrial Fibrillation.

    PubMed

    Jacobs, Victoria; May, Heidi T; Bair, Tami L; Crandall, Brian G; Cutler, Michael J; Day, John D; Mallender, Charles; Osborn, Jeffrey S; Stevens, Scott M; Weiss, J Peter; Woller, Scott C; Bunch, T Jared

    2016-07-15

    Direct oral anticoagulants (DOACs) have been used in clinical practice in the United States for the last 4 to 6 years. Although DOACs may be an attractive alternative to warfarin in many patients, long-term outcomes of use of these medications are unknown. We performed a propensity-matched analysis to report patient important outcomes of death, stroke/transient ischemic attack (TIA), bleeding, major bleeding, and dementia in patients taking a DOAC or warfarin. Patients receiving long-term anticoagulation from June 2010 to December 2014 for thromboembolism prevention with either warfarin or a DOAC were matched 1:1 by index date and propensity score. Multivariable Cox hazard regression was performed to determine the risk of death, stroke/TIA, major bleed, and dementia by the anticoagulant therapy received. A total of 5,254 patients were studied (2,627 per group). Average age was 72.4 ± 10.9 years, and 59.0% were men. Most patients were receiving long-term anticoagulation for AF management (warfarin: 96.5% vs DOAC: 92.7%, p <0.0001). Rivaroxaban (55.3%) was the most commonly used DOAC, followed by apixaban (22.5%) and dabigatran (22.2%). The use of DOACs compared with warfarin was associated with a reduced risk of long-term adverse outcomes: death (p = 0.09), stroke/TIA (p <0.0001), major bleed (p <0.0001), and bleed (p = 0.14). No significant outcome variance was noted in DOAC-type comparison. In the AF multivariable model patients taking DOAC were 43% less likely to develop stroke/TIA/dementia (hazard ratio 0.57 [CI 0.17, 1.97], p = 0.38) than those taking warfarin. Our community-based results suggest better long-term efficacy and safety of DOACs compared with warfarin. DOAC use was associated with a lower risk of cerebral ischemic events and new-onset dementia. PMID:27236255

  10. Perioperative venous thromboembolic disease and the emerging role of the novel oral anticoagulants: An analysis of the implications for perioperative management

    PubMed Central

    Mookadam, Martina; Shamoun, Fadi E.; Ramakrishna, Harish; Obeid, Hiba; Rife, Renee L.; Mookadam, Farouk

    2015-01-01

    Venous thromboembolism includes 2 inter-related conditions: Deep venous thrombosis and pulmonary embolism. Heparin and low-molecular-weight heparin followed by oral anticoagulation with vitamin K agonists is the first line and current accepted standard therapy with good efficacy. However, this therapeutic strategy has many limitations including the significant risk of bleeding and drug, food and disease interactions that require frequent monitoring. Dabigatran, rivaroxaban, apixaban, and edoxaban are the novel oral anticoagulants that are available for use in stroke prevention in atrial fibrillation and for the treatment and prevention of venous thromboembolism (HYPERLINK\\l ”1). Recent prospective randomized trials comparing the NOACs with warfarin have shown similar efficacy between the treatment strategies but fewer bleeding episodes with the NOACs. This paper presents an evidence-based review describing the efficacy and safety of the new anticoagulants compared to warfarin. PMID:26440238

  11. Perioperative venous thromboembolic disease and the emerging role of the novel oral anticoagulants: an analysis of the implications for perioperative management.

    PubMed

    Mookadam, Martina; Shamoun, Fadi E; Ramakrishna, Harish; Obeid, Hiba; Rife, Renee L; Mookadam, Farouk

    2015-01-01

    Venous thromboembolism includes 2 inter-related conditions: Deep venous thrombosis and pulmonary embolism. Heparin and low-molecular-weight heparin followed by oral anticoagulation with vitamin K agonists is the first line and current accepted standard therapy with good efficacy. However, this therapeutic strategy has many limitations including the significant risk of bleeding and drug, food and disease interactions that require frequent monitoring. Dabigatran, rivaroxaban, apixaban, and edoxaban are the novel oral anticoagulants that are available for use in stroke prevention in atrial fibrillation and for the treatment and prevention of venous thromboembolism (HYPERLINK\\l "1). Recent prospective randomized trials comparing the NOACs with warfarin have shown similar efficacy between the treatment strategies but fewer bleeding episodes with the NOACs. This paper presents an evidence-based review describing the efficacy and safety of the new anticoagulants compared to warfarin. PMID:26440238

  12. Clinical experience with the new oral anticoagulants for treatment of venous thromboembolism.

    PubMed

    Bacchus, Farzana; Schulman, Sam

    2015-03-01

    Four non-vitamin K antagonist oral anticoagulants, apixaban, dabigatran, edoxaban, and rivaroxaban, have been evaluated in phase III clinical trials for the treatment of acute venous thromboembolism, and all except edoxaban have also been studied for extended secondary prophylaxis after venous thromboembolism. Rivaroxaban, and recently also dabigatran, has been approved for this indication, and it is therefore timely to review the characteristics, efficacy, and safety of these drugs with emphasis on patients with venous thromboembolism. This review focuses on the clinical results from the phase III trials, separately for each of the drugs as compared with vitamin K antagonists. We also address the results from meta-analyses that were published recently. Finally, the results in some special groups of interest-renal impairment, elderly patients, and patients with cancer-are reviewed, although they only comprised small minorities of the study populations. All 4 drugs demonstrated noninferiority against vitamin K antagonists in the acute treatment and clear superiority against placebo in the extended treatment (not performed with edoxaban). The risk of bleeding was generally lower with non-vitamin K antagonist oral anticoagulants, and the reduction of risk of intracranial hemorrhage seems to mirror the experience from atrial fibrillation trials. In conclusion, during the past 30 years we have moved from a week of hospitalization and intravenous heparin therapy, via low-molecular-weight heparin injections subcutaneously and early discharge from the hospital, to the possibility of only oral outpatient therapy without coagulation monitoring, yet safe for patients with acute venous thromboembolism. PMID:25717178

  13. Expanding use of new oral anticoagulants

    PubMed Central

    2014-01-01

    New, non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. These include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. In the US, rivaroxaban and apixaban are licensed for thromboprophylaxis after elective hip or knee arthroplasty, and rivaroxaban and dabigatran are approved for treatment of venous thromboembolism. Dabigatran, rivaroxaban, and apixaban also are licensed for stroke prevention in eligible patients with atrial fibrillation. Designed to be given in fixed doses without routine coagulation monitoring, the NOACs are more convenient to administer than warfarin. Phase III clinical trials have shown that the NOACs are at least as effective as warfarin and are associated with less intracranial bleeding. This article compares the pharmacological properties of the NOACs with those of warfarin, describes the clinical trial data with the NOACs in the approved indications, outlines the unmet medical needs that the NOACs address, highlights the potential limitations of the NOACs, and provides guidance on the optimal use of the NOACs. PMID:25374671

  14. New Oral Anticoagulants and Their Reversal.

    PubMed

    Pinto, Ian; Giri, Anshu; Arshad, Umbreen; Gajra, Ajeet

    2015-01-01

    The advent of new oral anticoagulants (NOAC) has increased the armamentarium against thromboembolic diseases but has given rise to a conundrum on their reversal. NOAC's have comparable efficacy to traditional vitamin K antagonists with similar rates of major bleeding. However there is no standardized method for reversal of these agents and no specific antidote. This is of concern not only in acute bleeding episodes but also in clinical scenarios where emergency surgery is required. Recent studies have investigated reversal of dabigatran, rivaroxaban, and apixaban using prothrombin complex concentrates (PCC), recombinant factor VIIa, and in the case of dabigatran, a monoclonal antibody. These studies have been encouraging in showing improvement of bleeding times and blood loss in most models, especially with the use of PCCs and the dabigatran antibody. Of note the majority of common currently used coagulation assays may not correlate with clinical reversal. The management of overt bleeding with NOACs is difficult due to the lack of clinical trials. Current animal trials, case reports and hemostatic testing on human blood have shown some promise; provide guidance but warrant further investigation. PMID:25877809

  15. A review of the safety of anticoagulants in older people using the medicines management pathway: weighing the benefits against the risks

    PubMed Central

    2011-01-01

    Anticoagulant drugs maintain a high potential for adverse events due to their inherent risk of haemorrhage and/or complex pharmacology. In addition, compromising the safety of these agents is the context in which they are principally used; that is, in the long-term prevention of thromboembolic diseases in an older patient population. These challenges are especially pronounced in the prevention of stroke in older persons with atrial fibrillation (AF), where the need for thromboprophylaxis is paramount and in whom the arrhythmia is most prevalent, but where the target population is simultaneously at high risk of adverse drug events. Essentially, this translates to the use of high-risk therapies on an indefinite basis, in persons who have multiple comorbidities, use polypharmacy, and who may have age-related functional and cognitive decline, culminating in a higher potential for medication misadventure. For this reason, anticoagulants mandate extra pharmacovigilance, and therefore the aim of this review is to address some of the key safety considerations in the use of anticoagulant drugs (warfarin, dabigatran, rivaroxaban), spanning the initiation of therapy to its ongoing management. Using the Medication Management Pathway (MMP) as a framework, in this review we canvas and highlight specific developments in practical strategies to facilitate the safe use of anticoagulants (particularly warfarin) in ‘at-risk' elderly patients including: comprehensive risk/benefit assessment using novel risk stratification tools; focused medicines review services; therapeutic drug monitoring services delivered in the primary care setting; and practical education strategies and resources targeting the older patient population. Until newer alternative anticoagulants become viable options for widespread use, clinicians will necessarily need to rely on specific resources and interventions to facilitate the safe use of currently available anticoagulants (i.e. warfarin) in

  16. The polyphosphate/factor XII pathway in cancer-associated thrombosis: novel perspectives for safe anticoagulation in patients with malignancies.

    PubMed

    Nickel, Katrin F; Labberton, Linda; Long, Andrew T; Langer, Florian; Fuchs, Tobias A; Stavrou, Evi X; Butler, Lynn M; Renné, Thomas

    2016-05-01

    Cancer is an established risk factor for venous thromboembolism (VTE) and VTE is the second leading cause of death in patients with cancer. The incidence of cancer-related thrombosis is rising and is associated with worse outcomes. Despite our growing understanding on tumor-driven procoagulant mechanisms including cancer-released procoagulant proteases, expression of tissue factor on cancer cells and derived microvesicles, as well as alterations in the extracellular matrix of the cancer cell milieu, anticoagulation therapy in cancer patients has remained challenging. This review comments on a newly discovered cancer-associated procoagulant pathway. Experimental VTE models in mice and studies on patient cancer material revealed that prostate cancer cells and associated exosomes display the inorganic polymer polyphosphate on their plasma membrane. Polyphosphate activates blood coagulation factor XII and initiates thrombus formation via the intrinsic pathway of coagulation. Pharmacologic inhibition of factor XII activity protects mice from VTE and reduces thrombin coagulant activity in plasma of prostate cancer patients. Factor XII inhibitors provide thrombo-protection without impairing hemostatic mechanisms and thus, unlike currently used anticoagulants, do not increase bleeding risk. Interference with the polyphosphate/factor XII pathway may provide the novel opportunity for safe anticoagulation therapy in patients with malignancies. PMID:27207422

  17. Approach to the new oral anticoagulants in family practice

    PubMed Central

    Douketis, James; Bell, Alan David; Eikelboom, John; Liew, Aaron

    2014-01-01

    Abstract Objective To address common “what if” questions that arise relating to the long-term clinical follow-up and management of patients receiving the new oral anticoagulants (NOACs). Sources of information For this narrative review, we searched the PubMed database for recent (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for stroke prevention in atrial fibrillation and for the treatment of acute venous thromboembolism. We used this evidence base to address prespecified questions relating to NOAC use in primary care settings. Main message Dabigatran and rivaroxaban should be taken with meals to decrease dyspepsia and increase absorption, respectively. There are no dietary restrictions with any of the NOACs, beyond moderating alcohol intake, and rivaroxaban and apixaban can be crushed if required. The use of acid suppressive therapies does not appear to affect the efficacy of the NOACs. As with warfarin, patients taking NOACs should avoid long-term use of nonsteroidal anti-inflammatory and antiplatelet drugs. For patients requiring surgery, generally NOACs should be stopped 2 to 5 days before the procedure, depending on bleeding risk, and the NOAC should usually be resumed at least 24 hours after surgery. Preoperative coagulation testing is generally unnecessary. In patients who develop bleeding, minor bleeding typically does not require laboratory testing or discontinuation of NOACs; with major bleeding, the focus should be on local measures to control the bleeding and supportive care, and coagulation testing should be performed. There are currently no antidotes to reverse NOACs. The NOACs should not be used in patients with valvular heart disease, prosthetic heart valves, cancer-associated deep vein thrombosis, or superficial thrombophlebitis. Conclusion Management of “what if” scenarios for patients taking NOACs have been proposed, but additional study is needed to address these issues, especially periprocedural management and

  18. Simplified citrate anticoagulation for high-flux hemodialysis.

    PubMed

    Apsner, R; Buchmayer, H; Lang, T; Unver, B; Speiser, W; Sunder-Plassmann, G; Hörl, W H

    2001-11-01

    In a randomized crossover trial, we compared a simple citrate anticoagulation protocol for high-flux hemodialysis with standard anticoagulation by low-molecular-weight heparin (dalteparin). Primary end points were urea reduction rate (URR), Kt/V, and control of electrolyte and acid-base homeostasis. Secondary end points were bleeding time at vascular puncture sites and markers of activation of platelets, coagulation, and fibrinolysis. Solute removal during citrate dialysis was excellent (URR, 0.71 +/- 0.06; Kt/V, 1.55 +/- 0.3) and similar to results of conventional bicarbonate hemodialysis anticoagulation with dalteparin (URR, 0.72 +/- 0.04; Kt/V, 1.56 +/- 0.2). Electrolyte control was effective with both anticoagulation regimens, and total and ionized calcium, sodium, potassium, and phosphate concentrations at the end of dialysis did not differ. Alkalemia was less frequent after citrate than conventional dialysis (pH 7.5 in 25% versus 62% of patients; mean pH at end of dialysis, 7.46 +/- 0.06 versus 7.51 +/- 0.07; P < 0.01). Bleeding time at puncture sites was shorter by 30% after citrate compared with dalteparin anticoagulation (5.43 +/- 2.80 versus 7.86 +/- 2.93 minutes; P < 0.001). Activation of platelets, coagulation, and fibrinolysis was modest for both treatments and occurred mainly within the dialyzer during dalteparin treatment and in the vascular-access region during citrate anticoagulation. Citrate-related adverse events were not observed. We conclude that citrate anticoagulation for high-flux hemodialysis is feasible and safe using a simple infusion protocol. PMID:11684550

  19. Haemorrhagic complications of peripartum anticoagulation: A retrospective chart review

    PubMed Central

    Wang, Erica HZ; Marnoch, Catherine A; Khurana, Rshmi; Sia, Winnie

    2014-01-01

    Background Women with venous thromboembolism (VTE), thrombophilias or mechanical heart valves may require anticoagulation during pregnancy and postpartum. The incidence of postpartum hemorrhage (PPH) in the literature is 2.9–6%, but the rate while on anticoagulation is not well documented. Aims To determine the incidence of haemorrhagic complications associated with the use of peripartum anticoagulation, and the types and risk factors for haemorrhagic complications. Methods A retrospective chart review was conducted on women who delivered at an academic teaching hospital and received peripartum anticoagulation between January 2000 and August 2009. Women with known bleeding disorders were excluded. Results In total, 195 cases were identified with mean age 31.3 years and gestational age of 37.7 weeks. Of these, 49% had a history of VTE, 21% had active VTE in the index pregnancy, and 63% had vaginal delivery. Types of anticoagulation used antepartum were unfractionated heparin (UFH) (43%) and low molecular weight heparin (LMWH) (36%), with 26% receiving therapeutic doses. The rate of haemorrhagic complications was 12.8%, with majority being PPH (80%). Sixty percent of the PPH occurred before reintroduction of anticoagulation postpartum. Use of therapeutic UFH antepartum was associated with increased risk of haemorrhagic complications compared to LMWH (OR 3.08, 95% CI 0.663 – 15.03, p = 0.183). Conclusion The rate of haemorrhagic complications is higher in women on peripartum anticoagulation compared with published incidence in unselected obstetric populations; however, this rate is similar to our institution’s reported rates. Our findings inform clinicians about competing risks of thrombotic and haemorrhagic complications in this population.

  20. Antiplatelet Therapy During PCI for Patients with Stable Angina and Atrial Fibrillation.

    PubMed

    Iqbal, Amjid; Rodriguez, Fatima; Schirmer, Henrik

    2015-08-01

    The pharmacological treatment options for anticoagulation in patients with atrial fibrillation (Afib) have increased with the introduction of novel oral anticoagulants, compared with earlier times, when vitamin K antagonist was the drug of choice. As they age, many Afib patients require percutaneous coronary intervention (PCI), necessitating antiplatelet medication in addition to anticoagulation therapy. Choosing the appropriate combination and duration of anticoagulation and antiplatelet therapies may be challenging in stable coronary artery disease (CAD) and even more complicated during and after coronary intervention with the introduction of additional antithrombotic drugs. In this article, we review the scientific basis for the recent guidelines for anticoagulation and antithrombotic therapy in patients with Afib and stable CAD before, during, and after elective PCI. PMID:26104508

  1. The Role of Nonvitamin K Antagonist Oral Anticoagulants (NOACs) in Stroke Prevention in Patients with Atrial Fibrillation.

    PubMed

    Kuznetsov, Sofya; Barcelona, Robert; Josephson, Richard A; Mohan, Sri K Madan

    2016-05-01

    Anticoagulation is important in stroke prevention in patients with atrial fibrillation. Until recently, heparins and vitamin K antagonists were the only available therapy for stroke reduction in atrial fibrillation (AF) patients. Non-vitamin K antagonist oral anticoagulants (NOACs) including direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) are now available and offer new options for stroke prevention. This article reviews the available data on the use of NOACs for primary and secondary stroke prevention in AF patients and describes specific patient populations to guide clinician in making the informed decision regarding appropriate use of those agents. It also addresses the use of NOACs early after acute stroke and use of thrombolysis while on NOAC. PMID:27023335

  2. Anticoagulation Management and Monitoring during Pediatric Extracorporeal Life Support: A Review of Current Issues

    PubMed Central

    Ryerson, Lindsay M.; Lequier, Laurence L.

    2016-01-01

    Anticoagulation is an imperfect science and is even more complicated in neonates and young children. The addition of the extracorporeal life support (ECLS) foreign circuit adds an additional layer of complexity. Anticoagulation goals during ECLS are to maintain a clot-free circuit and a hemostatically balanced patient. Unfractionated heparin (UFH) is the default gold standard anticoagulant as no large studies have been performed on any other anticoagulants. This review will focus on the advantages and disadvantages of the various methods to monitor UFH anticoagulation, discuss alternative anticoagulants, and examine bleeding and thrombotic complications during ECLS.

  3. Anticoagulation for the prevention of stroke in non-valvular AF in general practice: room for improvement

    PubMed Central

    Ioannou, Adam; Metaxa, Sofia; Kassianos, George; Missouris, Constantinos G.

    2016-01-01

    Objective: Our aim was to assess whether the recommendations and guidelines for thromboprophylaxis in patients with atrial fibrillation (AF) have been adopted in general practice (GP). Methods: We conducted a retrospective study using the GP computer database (Hatfield, UK) on all 9400 patients to assess the quality of anticoagulation in patients with a recorded diagnosis of AF. Results: Of the 180 patients with a diagnosis of AF, 107 (59.4%) were treated with warfarin, 19 (10.6%) with a novel oral anticoagulant (NOAC), 31 (17.2%) with aspirin or clopidogrel, and 23 (12.8%) received none. Thirty-seven patients (34.6%) who were taking warfarin had a time in the therapeutic range (TTR) of less than 65%. Forty-five (27.6%) of the 163 patients who had a CHA2DS2VASc score of two or more were not prescribed a vitamin K antagonist (VKA) or a NOAC. None had a HAS-BLED greater than the CHA2DS2VASc score. Conclusion: Our study demonstrates that one in four patients with non-valvular AF, at risk of a stroke, is not being adequately treated with an oral anticoagulant in primary care. The majority were treated with warfarin, a third of which had a low TTR. A high proportion of patients are prescribed antiplatelet therapy instead. This is despite overwhelming evidence that VKAs and NOACs, and not aspirin or clopidogrel, improve outcome in patients with non-valvular AF. We suggest that a review of GP practice databases should be considered to identify patients with non-valvular AF, at risk of a disabling or fatal event, and measures taken to initiate anticoagulant therapy. PMID:27403193

  4. Low-Dose Heparin Anticoagulation During Extracorporeal Life Support for Acute Respiratory Distress Syndrome in Conscious Sheep

    PubMed Central

    Prat, Nicolas J.; Meyer, Andrew D.; Langer, Thomas; Montgomery, Robbie K.; Parida, Bijaya K.; Batchinsky, Andriy I.; Cap, Andrew P.

    2015-01-01

    ABSTRACT Background: Over 32% of burned battlefield causalities develop trauma-induced hypoxic respiratory failure, also known as acute respiratory distress syndrome (ARDS). Recently, 9 out of 10 US combat soldiers’ survived life-threatening trauma-induced ARDS supported with extracorporeal membrane oxygenation (ECMO), a portable form of cardiopulmonary bypass. Unfortunately, the size, incidence of coagulation complications, and the need for systematic anticoagulation for traditional ECMO devices have prevented widespread use of this lifesaving technology. Therefore, a compact, mobile, ECMO system using minimal anticoagulation may be the solution to reduce ARDS in critically ill military and civilian patients. Methods: We conducted a prospective cohort laboratory investigation to evaluate the coagulation function in an ovine model of oleic acid induced ARDS supported with veno-venous ECMO. The experimental design approximated the time needed to transport from a battlefield setting to an advanced facility and compared bolus versus standard heparin anticoagulation therapy. Results: Comprehensive coagulation and hemostasis assays did not show any difference because of ECMO support over 10 h between the two groups but did show changes because of injury. Platelet count and function did decrease with support on ECMO, but there was no significant bleeding or clot formation during the entire experiment. Conclusions: A bolus heparin injection is sufficient to maintain ECMO support for up to 10 h in an ovine model of ARDS. With a reduced need for systematic anticoagulation, ECMO use for battlefield trauma could reduce significant morbidity and mortality from ventilator-induced lung injury and ARDS. Future studies will investigate the mechanisms and therapies to support patients for longer periods on ECMO without coagulation complications. Level of Evidence: V—therapeutic animal experiment. PMID:26263439

  5. Mid-Term Outcome of Mechanical Pulmonary Valve Prostheses: The Importance of Anticoagulation

    PubMed Central

    Sadeghpour, Anita; Kyavar, Majid; Javani, Bahareh; Bakhshandeh, Hooman; Maleki, Majid; Khajali, Zahra; Subrahmanyan, Lakshman

    2014-01-01

    Introduction: Pulmonary valve replacement (PVR) is being performed more commonly late after the correction of tetralogy of Fallot. Most valves are replaced with an allograft or xenograft, although reoperations are a common theme. Mechanical prostheses have a less favorable reputation due to the necessity of lifelong anticoagulation therapy and higher risk of thrombosis, but they are also less likely to require reoperation. There is a paucity of data on the use of prosthetic valves in the pulmonary position. We report the midterm outcomes of 38 cases of PVR with mechanical prostheses. Methods: One hundred twenty two patients who underwent PVR were studied. Thirty-eight patients, mean age 25 ± 8.4 years underwent PVR with mechanical prostheses based on the right ventricular function and the preferences of the patients and physicians. Median age of prosthesis was 1 year (range 3 months to 5 years). Results: Seven (18%) patients had malfunctioning pulmonary prostheses and two patients underwent redo PVR. Mean International Normalized Ratio (INR) in these seven patients was 2.1±0.8. Fibrinolytic therapy was tried and five of them responded to it well. There was no significant association between the severity of right ventricular dysfunction, patient’s age, prostheses valve size and age of the prosthesis in the patients with prosthesis malfunction. Conclusion: PVR with mechanical prostheses can be performed with promising midterm outcomes. Thrombosis on mechanical pulmonary valve prostheses remains a serious complication, but most prosthesis malfunction respond to fibrinolytic therapy, underscoring the need for adequate anticoagulation therapy. PMID:25320663

  6. Survey of Botulinum Toxin Injections in Anticoagulated Patients: Korean Physiatrists' Preference in Controlling Anticoagulation Profile Prior to Intramuscular Injection

    PubMed Central

    Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P.; Ismail, Farooq

    2016-01-01

    Objective To evaluate Korean physiatrists' practice of performing intramuscular botulinum toxin injection in anticoagulated patients and to assess their preference in controlling the bleeding risk before injection. Methods As part of an international collaboration survey study, a questionnaire survey was administered to 100 Korean physiatrists. Physiatrists were asked about their level of experience with botulinum toxin injection, the safe international normalized ratio range in anticoagulated patients undergoing injection, their tendency for injecting into deep muscles, and their experience of bleeding complications. Results International normalized ratio <2.0 was perceived as an ideal range for performing Botulinum toxin injection by 41% of the respondents. Thirty-six respondents replied that the international normalized ratio should be lowered to sub-therapeutic levels before injection, and 18% of the respondents reported that anticoagulants should be intentionally withheld and discontinued prior to injection. In addition, 20%–30% of the respondents answered that they were uncertain whether they should perform the injection regardless of the international normalized ratio values. About 69% of the respondents replied that they did have any standardized protocols for performing botulinum toxin injection in patients using anticoagulants. Only 1 physiatrist replied that he had encountered a case of compartment syndrome. Conclusion In accordance with the lack of consensus in performing intramuscular botulinum toxin injection in anticoagulated patients, our survey shows a wide range of practices among many Korean physiatrists; they tend to avoid botulinum toxin injection in anticoagulated patients and are uncertain about how to approach these patients. The results of this study emphasize the need for formulating a proper international consensus on botulinum toxin injection management in anticoagulated patients. PMID:27152278

  7. Hepatotoxicity of New Oral Anticoagulants (NOACs).

    PubMed

    Liakoni, Evangelia; Rätz Bravo, Alexandra E; Krähenbühl, Stephan

    2015-08-01

    Case reports and analyses of clinical studies and of pharmacovigilance data suggest that new oral anticoagulants (NOACs) are associated with a small risk for hepatotoxicity. The objective of this publication is to summarize the current data about this subject, with a special emphasis on pharmacovigilance data in the World Health Organization (WHO) Global Individual Case Safety Reports (ICSR) database and on potential mechanisms of hepatotoxicity. For that, all available case reports as well as published analyses of clinical studies were obtained with a detailed search in PubMed. In addition, pharmacovigilance data from VigiBase(®), the WHO Global ICRS database, were extracted and analyzed. The data show that liver injury associated with NOACs was reported in clinical studies and in pharmacovigilance databases. Several case reports described potentially life-threatening hepatotoxicity in patients treated with rivaroxaban or dabigatran. For rivaroxaban, most affected patients were symptomatic and liver injury was most often hepatocellular or mixed. The frequency was between 0.1 and 1 % in clinical studies and was by trend lower than for comparators (mostly enoxaparin or warfarin). Comparing the pharmacovigilance reports for the individual NOACs, more hepatic adverse events were reported for rivaroxaban than for dabigatran or apixaban. With the exception of edoxaban, for which only few reports are available, patients with acute liver failure have been reported for every NOAC, but most patients had concomitant drugs or diseases. So far, there are no clear mechanisms explaining the hepatotoxicity of these drugs. We conclude that hepatotoxicity appears to be associated with all NOACs currently on the market. Hepatotoxicity associated with NOACs is idiosyncratic; it appears at therapeutic doses, is rare and the mechanism is not related to the pharmacological action of these drugs. Prescribers should inform patients about possible symptoms of hepatotoxicity and stop these

  8. Resident Physicians Choices of Anticoagulation for Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation.

    PubMed

    Oqab, Zardasht; McIntyre, William F; Quinn, Kieran L; Lamb, Tyler; Quadros, Kenneth; Yazdan-Ashoori, Payam; van Oosten, Erik; Chu, Karen; Lamba, Jasmine; Barake, Walid; Mohajer, Kiarash; Marr, Jeffrey N; Baranchuk, Adrian

    2016-06-01

    Atrial fibrillation (AF) is a common cardiac arrhythmia and is associated with an increased risk of ischemic stroke. The aim of this study was to identify practice patterns of Canadian resident physicians pertaining to stroke prevention in nonvalvular AF according to the Canadian Cardiovascular Society guidelines. A Web-based survey consisting of 16 multiple-choice questions was distributed to 11 academic centres. Questions involved identification of risks of stroke, bleeding, and selection of appropriate therapy in clinical scenarios that involve a patient with AF with a Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack (CHADS2) score of 3 and no absolute contraindications to anticoagulation. There were 1014 total respondents, of whom 570 were internal, 247 family, 137 emergency medicine, and 60 adult cardiology residents. For a patient with a new diagnosis of AF, warfarin was chosen by 80.3%, novel oral anticoagulants (NOACs) by 60.3%, and acetylsalicylic acid (ASA) by 7.2% of residents. To a patient with a history of gastrointestinal bleed during ASA treatment, warfarin was recommended by 75.1%, NOACs by 36.1%, ASA by 12.1%, and 4% were unsure. For a patient with a history of an intracranial bleed, warfarin was recommended by 38.8%, NOACs by 23%, ASA by 24.8%, and 18.2% were unsure. For a patient taking warfarin who had a labile international normalized ratio, 89% would switch to a NOAC and 29.5% would continue warfarin. This study revealed that, across a wide sampling of disciplines and centres, resident physician choices of anticoagulation in nonvalvular AF differ significantly from contemporary Canadian Cardiovascular Society guidelines. PMID:26652126

  9. Anticoagulant rodenticide poisoning in animals of Apulia and Basilicata, Italy.

    PubMed

    Muscarella, Marilena; Armentano, Antonio; Iammarino, Marco; Palermo, Carmen; Amorena, Michele

    2016-06-30

    This study evaluates the presence of anticoagulant rodenticides in animals with a diagnosis of suspected poisoning and in bait samples. The survey was carried out from 2010 to 2012, in 2 regions of South Italy (Puglia and Basilicata) on 300 organs of animals and 90 suspected bait samples. The qualitative and quantitative analyses were conducted using an analytical method based on high‑performance liquid chromatography (HPLC) with fluorimetric detection (FLD) for the simultaneous determination of 8 anticoagulant rodenticides (bromadiolone, brodifacoum, coumachlor, coumafuryl, coumatetralyl, difenacoum, flocoumafen, and warfarin). The presence of anticoagulant rodenticides was detected in 33 organs of animals (11% of the total) and 6 bait samples (7% of the total). The most commonly detected compound was coumachlor (47% of 39 positive samples) followed by bromadiolone (24%), and brodifacoum (11%). The species mostly involved in anticoagulant rodenticide poisoning were dogs and cats. This study emphasizes the relevance of the determinations of anticoagulant rodenticides in cases of suspected poisoning in veterinary practice. PMID:27393877

  10. Anticoagulant proteins from snake venoms: structure, function and mechanism

    PubMed Central

    Kini, R. Manjunatha

    2006-01-01

    Over the last several decades, research on snake venom toxins has provided not only new tools to decipher molecular details of various physiological processes, but also inspiration to design and develop a number of therapeutic agents. Blood circulation, particularly thrombosis and haemostasis, is one of the major targets of several snake venom proteins. Among them, anticoagulant proteins have contributed to our understanding of molecular mechanisms of blood coagulation and have provided potential new leads for the development of drugs to treat or to prevent unwanted clot formation. Some of these anticoagulants exhibit various enzymatic activities whereas others do not. They interfere in normal blood coagulation by different mechanisms. Although significant progress has been made in understanding the structure–function relationships and the mechanisms of some of these anticoagulants, there are still a number of questions to be answered as more new anticoagulants are being discovered. Such studies contribute to our fight against unwanted clot formation, which leads to death and debilitation in cardiac arrest and stroke in patients with cardiovascular and cerebrovascular diseases, arteriosclerosis and hypertension. This review describes the details of the structure, mechanism and structure–function relationships of anticoagulant proteins from snake venoms. PMID:16831131

  11. Anticoagulation management in mechanical circulatory support

    PubMed Central

    Bennett, Mosi K.

    2015-01-01

    Heart failure continues to be a worldwide epidemic, effecting over 23 million persons. Despite advances in medical therapy, the disease is progressive and a significant proportion of patients will need advanced heart replacement therapy. Continuous flow assist devices have become a standard approach for many patients both as a bridge to cardiac transplantation and as destination therapy (DT). However, device related complications such as bleeding and thrombosis continue to hinder further advancements of this technology. The field is rapidly advancing and efforts to reduce pump complications are directed towards improving hemocompatibility and maximizing blood flow without clinically significant hemolysis, areas of stasis or turbulent flow. PMID:26793333

  12. [Managing antithrombotic therapy in vitreoretinal surgery].

    PubMed

    Gallice, M; Rouberol, F; Albaladejo, P; Brillat Zaratzian, E; Palombi, K; Aptel, F; Romanet, J-P; Chiquet, C

    2015-01-01

    Given the growing number of patients on antithrombotic therapy we are increasingly confronted with the management of this therapy before, during and after vitreoretinal surgery. In the absence of a consensus, the decision to withdraw antithrombotic therapy is based on the cardiovascular thromboembolism risk versus the theoretical risk of bleeding if the antithrombotic treatment is continued. As suggested by the literature, antiplatelet therapy (acetylsalicylic acid or clopidogrel) may be safely continued for vitreoretinal surgery, including retinal detachment repair. However, the risk/benefit ratio for patients being treated with two antiplatelet therapies is unknown. It appears that an International Normalized Ratio (INR) less than 3 for patients treated with anticoagulant therapy does not increase the perioperative risk of ocular bleeding. This risk has not been evaluated in patients treated by new antithrombotic therapies (prasugrel, ticagrelor as antiplatelet medication, or dabigatran, rivaroxaban, apixaban as anticoagulant therapy), and there is a need to study it further. PMID:25577431

  13. Pharmacokinetic and pharmacodynamic properties of oral anticoagulants, especially phenprocoumon.

    PubMed

    Haustein, K O

    1999-01-01

    Anticoagulants of the cumarin-type (warfarin, phenprocoumon, and acenocoumarol) are drugs for the long-term treatment and prevention of thromboembolic disorders. Because of their narrow therapeutic range, many patients have bleedings of variable severity or have recurrent thrombotic events. For this reason, the study of the pharmacokinetic parameters of phenprocoumon (PPC), considering its influence on blood clotting factors, is of high interest. The elimination kinetics of PPC, its interaction with phytomenadion (vitamin K), and the pharmacokinetic behavior of the anticoagulant under steady-state conditions have been investigated in studies with healthy volunteers and patients taking anticoagulants. The maintenance dose and the plasma levels of PPC were correlated with prothrombin time (PT) in 89 patients treated with PPC. Varying parameters in each patient (e.g., elimination kinetics of PPC, activity of the cumarin-dependent blood-clotting factors, endogenous phytomenadion stores), render it impossible to use a different means of monitoring than that of PT determination. PMID:10327214

  14. Management of Periprocedural Anticoagulation: A Survey of Contemporary Practice.

    PubMed

    Flaker, Greg C; Theriot, Paul; Binder, Lea G; Dobesh, Paul P; Cuker, Adam; Doherty, John U

    2016-07-12

    Interruption of oral anticoagulation (AC) for surgery or an invasive procedure is a complicated process. Practice guidelines provide only general recommendations, and care of such patients occurs across multiple specialties. The availability of direct oral anticoagulants further complicates decision making and guidance here is limited. To evaluate current practice patterns in the United States for bridging AC, a survey was developed by the American College of Cardiology Anticoagulation Work Group. The goal of the survey was to assess how general and subspecialty cardiologists, internists, gastroenterologists, and orthopedic surgeons currently manage patients who receive AC and undergo surgery or an invasive procedure. The survey was completed by 945 physicians involved in the periprocedural management of AC. The results provide a template for educational and research projects geared toward the development of clinical pathways and point-of-care tools to improve this area of health care. PMID:27386777

  15. Thrombotic and hemorrhagic complications in children with the lupus anticoagulant.

    PubMed

    Bernstein, M L; Salusinsky-Sternbach, M; Bellefleur, M; Esseltine, D W

    1984-12-01

    Endogenous circulating anticoagulants are unusual in children without a congenital factor deficiency. In particular, the lupus anticoagulant has only rarely been reported in children. Despite its functioning in vitro to prolong the partial thromboplastin time, patients more frequently have problems with thrombosis than bleeding, unless there is a coexistent prothrombin deficiency or thrombocytopenia. We report the cases of three children with the lupus anticoagulant. Two children had associated thromboses. One had a thrombosis of the iliofemoral system and the other had a partial Budd-Chiari syndrome, a thrombosis of the deep calf veins and ureteric obstruction. The third child had a concomitant prothrombin deficiency and bleeding after tooth extraction. Associated findings in these patients included a positive antinuclear antibody test in two, a positive anti-DNA antibody test in two, a false-positive VDRL test in two, and an antiphospholipid antibody test in two. PMID:6439032

  16. Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

    PubMed

    King, Nathan; Tran, Minh-Ha

    2015-10-01

    Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment

  17. Atrial fibrillation anticoagulation care in a large urban family medicine practice

    PubMed Central

    Valentinis, Alissia; Ivers, Noah; Bhatia, Sacha; Meshkat, Nazanin; Leblanc, Kori; Ha, Andrew; Morra, Dante

    2014-01-01

    anticoagulation and an additional 8.7% (6 of 69) had documented reasons why they were not taking anticoagulants. Conclusion When assessed using the 2012 Canadian Cardiovascular Society AF guidelines, the proportion of patients receiving appropriate SPAF therapy in this primary care setting decreased substantially. All patients with CHADS2 scores of 0 or 1 should be reassessed to ensure that they are receiving optimal stroke prevention treatment. PMID:24627401

  18. The efficacy and safety of different anticoagulants on patients with severe sepsis and derangement of coagulation: a protocol for network meta-analysis of randomised controlled trials

    PubMed Central

    Jiang, Libing; Jiang, Shouyin; Feng, Xia; Ma, Yuefeng; Zhang, Mao

    2014-01-01

    Introduction Sepsis is the leading cause of mortality in non-cardiological critically ill patients. There are as many as 20 million cases of sepsis annually worldwide, with a mortality rate of around 35%. It has been reported that the dysregulation of haemostatic system due to the interaction between coagulation system and inflammatory response is a strong predictor of mortality in patients with severe sepsis. In this context, several anticoagulants have been evaluated in recent years. However, the results of these studies were inconsistent and even contradictory. In addition, there is insufficient evidence comparing the efficacy and safety of different anticoagulants. The purpose of our study is to carry out a systematic review and network meta-analysis comparing the efficacy and safety of different anticoagulants for severe sepsis based on existing randomised controlled trials (RCTs) and ranking these anticoagulants for practical consideration. Methods and analysis PubMed, EMBASE and Cochrane Library databases will be systematically searched for eligible studies. Randomised controlled trials (RCT) on anticoagulant therapy for severe sepsis with multiple outcome measures will be included. The Cochrane Risk of Bias Tool will be used to assess the quality of included studies. The primary outcomes are mortality and bleeding events. The secondary outcomes include the length of intensive care stay, the length of hospital stay and duration of mechanical ventilation. Direct pairwise meta-analysis (DMA), indirect treatment comparison meta-analysis (ITC) and network meta-analysis (NMA) will be conducted to compare different anticoagulants. Ethics and dissemination Ethical approval is not required given that this is a protocol for a systematic review. The protocol of this systematic review will be disseminated in a peer-reviewed journal and presented at a relevant conference. Trial registration number This protocol has been registered in PROSPERO (http

  19. Achieved Anticoagulation vs Prosthesis Selection for Mitral Mechanical Valve Replacement

    PubMed Central

    Le Tourneau, Thierry; Lim, Vanessa; Inamo, Jocelyn; Miller, Fletcher A.; Mahoney, Douglas W.; Schaff, Hartzell V.; Enriquez-Sarano, Maurice

    2009-01-01

    Background: Thromboembolic events (TEs) are frequent after mechanical mitral valve replacement (MVR), but their association to anticoagulation quality is unclear and has never been studied in a population-based setting with patients who have a complete anticoagulation record. Methods: We compiled a complete record of all residents of Olmsted County, MN, who underwent mechanical MVR between 1981 and 2004, for all TE, bleeding episodes, and international normalized ratios (INRs) measured from prosthesis implantation. Results: In the 112 residents (mean [± SD] age, 57 ± 16 years; 60% female residents) who underwent mechanical MVR, 19,647 INR samples were obtained. While INR averaged 3.02 ± 0.57, almost 40% of INRs were < 2 or > 4.5. Thirty-four TEs and 28 bleeding episodes occurred during a mean duration of 8.2 ± 6.1 years of follow-up. There was no trend of association of INR (average, SD, growth variance rate, or intensity-specific incidence of events) with TE. Previous cardiac surgery (p = 0.014) and ball prosthesis (hazard ratio [HR], 2.92; 95% CI, 1.43 to 5.94; p = 0.003) independently determined TE. With MVR using a ball prosthesis, despite higher anticoagulation intensity (p = 0.002), the 8-year rate of freedom from TE was considerably lower (50 ± 9% vs 81 ± 5%, respectively; p < 0.0001). Compared with expected stroke rates in the population, stroke risk was elevated with non-ball prosthesis MVR (HR 2.6; 95% CI, 1.3 to 5.2; p = 0.007) but was considerable with ball prosthesis MVR (HR 11.7; 95% CI, 7.5 to 18.4; p < 0.0001). INR variability (SD) was higher with a higher mean INR value (p < 0.0001). INR variability (HR 2.485; 95% CI, 1.11 to 5.55; p = 0.027) and cancer history (p < 0.0001) independently determined bleeding rates. Conclusion: This population-based comprehensive study of anticoagulation and TE post-MVR shows that, in these closely anticoagulated patients, anticoagulation intensity was highly variable and not associated with TE incidence post

  20. Novel oral anticoagulants in the treatment of cerebral venous thrombosis.

    PubMed

    Feher, Gergely; Illes, Zsolt; Komoly, Samuel; Hargroves, David

    2016-08-01

    Cerebral venous thrombosis (CVT) is an uncommon cause of stroke with extremely diverse clinical features, predisposing factors, brain imaging findings, and outcome. Anticoagulation is the cornerstone of CVT management, however, it is not supported by high-quality evicence. Novel oral anticoagulants (NOACs) have been extensively studied in patients with deep vein thrombosis, pulmonary embolism and non-valvular atrial fibrillation. The aim of our work was to review the available evidence for NOACs in the treatment of CVT. Based on our literature search there is insufficient evidence to support the use of NOACs in CVT, although case series with rivaroxaban and dabigatran have showed promising results. PMID:25994451

  1. Comparative study of a portable prothrombin time monitor employing three different systems in oral anticoagulant units.

    PubMed

    Vacas, M; Fernández, M A; Martínez-Brotons, F; Lafuente, P J; Ripoll, F; Alvarez, C; Iriarte, J A

    2001-01-01

    The aim of this study was to evaluate the accuracy of the portable coagulometer CoaguChek (Roche Diagnostics) as a prothrombin time (PT) monitor, and to correlate capillary blood results with those of three different routine methods used for monitoring oral anticoagulant therapy (OAT): capillary, plasma and whole blood samples. Three hospitals participated in the study with a total of 235 patients on OAT. The international normalized ratio (INR) results obtained with CoaguChek were compared with those obtained using each of the routine methods. The study presents a good correlation between the PT monitor and the three methods studied: r = 0.9745 (hospital A), r = 0.9283 (hospital B), r = 0.9136 (hospital C). A simplified concordance test of the methods results in a nine-field comparison table showing concordances of 87.2, 85.7 and 68.4%, respectively. The absolute difference (mean +/- SD) between laboratory A and CoaguChek INRs was 0.0571 +/- 0.2042, with values of 0.04286 +/- 0.3906 for laboratory B and 0.6986 +/- 0.6170 for laboratory C. These results confirm that CoaguChek could be used as a new method for oral anticoagulant monitoring, and is in best agreement with the capillary blood PT system. PMID:11408745

  2. Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians

    PubMed Central

    Peacock, W. Frank; Rafique, Zubaid; Singer, Adam J.

    2016-01-01

    Nonvalvular atrial fibrillation- (NVAF-) related stroke and venous thromboembolism (VTE) are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs)—dabigatran, rivaroxaban, apixaban, and edoxaban—have been developed for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed. PMID:27293895

  3. CRRT Regional Anticoagulation Using Citrate in the Liver Failure and Liver Transplant Population.

    PubMed

    Wonnacott, Rob; Josephs, Brandi; Jamieson, Jill

    2016-01-01

    Regional citrate for continuous renal replacement therapy (CRRT) use in patients with liver failure or post-liver transplant has been considered a contraindication because of the risk of citrate toxicity development. Regional citrate has the benefit of decreased bleeding risks over systemic anticoagulation; therefore, it is of great benefit to the coagulopathic and surgical populations. This article analyzes current empiric data and compares with a case study specifically related to liver failure, liver transplant, and CRRT use. We found that the use of a total serum to ionized calcium ratio was much more reliable in measuring liver function than liver enzyme figures. This when paired with a citrate-reduction guideline based on serum to ionized calcium ratios provided effective, early management of citrate toxicity. Using new measurements to calculate liver metabolism of citrate and using a new citrate-reducing guideline allow the bedside practitioner to use regional citrate anticoagulation in patients with liver failure and liver transplant who require CRRT. PMID:27254640

  4. Anticoagulation in combination with antiangiogenesis and chemotherapy for cancer patients: evidence and hypothesis

    PubMed Central

    Wang, Ji; Zhu, Chengchu

    2016-01-01

    Hypercoagulable state and disorganized angiogenesis are two conspicuous characteristics during tumor progression. There are a considerable number of clinical trials focusing on the effects of anticoagulant and antiangiogenic drugs on the survival of cancer patients. Favorable outcomes have been observed. Excessive blood coagulation not only causes cancer-associated thrombosis, which is a common complication and is the second leading cause of death in patients, but also decreases intratumoral perfusion rates and drug delivery by reducing the effective cross-sectional area of blood vessels. Meanwhile, structural and functional abnormalities of the tumor microvasculature also compromise convective drug transport and create a hypoxic and acidic microenvironment. Vascular normalization strategy can temporarily recover the abnormal state of tumor vasculature by improving blood density, dilation, and leakiness, resulting in enhanced penetration of chemotherapies and oxygen within a short time window. In this article, we first review the evidence to support the opinion that anticoagulant and antiangiogenic therapy can improve cancer survival through several underlying mechanisms. Next, we speculate on the feasibility and value of the combined strategy and discuss whether such a combination has a synergistic antineoplastic effect in cancer patients by way of increasing blood vessel perfusion and drug distribution. PMID:27536135

  5. Exploring barriers to optimal anticoagulation for atrial fibrillation: interviews with clinicians

    PubMed Central

    Decker, Carole; Garavalia, Linda; Garavalia, Brian; Simon, Teresa; Loeb, Matthew; Spertus, John A; Daniel, William C

    2012-01-01

    Background Warfarin, the most commonly used antithrombotic agent for stroke prophylaxis in atrial fibrillation (AF), requires regular monitoring, frequent dosage adjustments, and dietary restrictions. Clinicians’ perceptions of barriers to optimal AF management are an important factor in treatment. Anticoagulation management for AF is overseen by both cardiology and internal medicine (IM) practices. Thus, gaining the perspective of specialists and generalists is essential in understanding barriers to treatment. We used qualitative research methods to define key issues in the prescription of warfarin therapy for AF by cardiology specialists and IM physicians. Methods and results Clinicians were interviewed to identify barriers to warfarin treatment in a large Midwestern city. Interviews were conducted until thematic saturation occurred. Content analysis yielded several themes. The most salient theme that emerged from clinician interviews was use of characteristics other than the patient’s CHADS2 score to enact a treatment plan, such as the patient’s social situation and past medication-taking behavior. Other themes included patient knowledge, real-world problems, breakdown in communication, and clinician reluctance. Conclusion Warfarin treatment is associated with many challenges. The barriers identified by clinicians highlight the unmet need associated with stroke prophylaxis in AF and the opportunity to improve anticoagulation treatment in AF. Social and lifestyle factors were important considerations in determining treatment. PMID:22936848

  6. Anticoagulation in combination with antiangiogenesis and chemotherapy for cancer patients: evidence and hypothesis.

    PubMed

    Wang, Ji; Zhu, Chengchu

    2016-01-01

    Hypercoagulable state and disorganized angiogenesis are two conspicuous characteristics during tumor progression. There are a considerable number of clinical trials focusing on the effects of anticoagulant and antiangiogenic drugs on the survival of cancer patients. Favorable outcomes have been observed. Excessive blood coagulation not only causes cancer-associated thrombosis, which is a common complication and is the second leading cause of death in patients, but also decreases intratumoral perfusion rates and drug delivery by reducing the effective cross-sectional area of blood vessels. Meanwhile, structural and functional abnormalities of the tumor microvasculature also compromise convective drug transport and create a hypoxic and acidic microenvironment. Vascular normalization strategy can temporarily recover the abnormal state of tumor vasculature by improving blood density, dilation, and leakiness, resulting in enhanced penetration of chemotherapies and oxygen within a short time window. In this article, we first review the evidence to support the opinion that anticoagulant and antiangiogenic therapy can improve cancer survival through several underlying mechanisms. Next, we speculate on the feasibility and value of the combined strategy and discuss whether such a combination has a synergistic antineoplastic effect in cancer patients by way of increasing blood vessel perfusion and drug distribution. PMID:27536135

  7. Neuraxial and peripheral nerve blocks in patients taking anticoagulant or thromboprophylactic drugs: challenges and solutions

    PubMed Central

    Li, Jinlei; Halaszynski, Thomas

    2015-01-01

    Incidence of hemorrhagic complications from neuraxial blockade is unknown, but classically cited as 1 in 150,000 epidurals and 1 in 220,000 spinals. However, recent literature and epidemiologic data suggest that for certain patient populations the frequency is higher (1 in 3,000). Due to safety concerns of bleeding risk, guidelines and recommendations have been designed to reduce patient morbidity/mortality during regional anesthesia. Data from evidence-based reviews, clinical series and case reports, collaborative experience of experts, and pharmacology used in developing consensus statements are unable to address all patient comorbidities and are not able to guarantee specific outcomes. No laboratory model identifies patients at risk, and rarity of neuraxial hematoma defies prospective randomized study so “patient-specific” factors and “surgery-related” issues should be considered to improve patient-oriented outcomes. Details of advanced age, older females, trauma patients, spinal cord and vertebral column abnormalities, organ function compromise, presence of underlying coagulopathy, traumatic or difficult needle placement, as well as indwelling catheter(s) during anticoagulation pose risks for significant bleeding. Therefore, balancing between thromboembolism, bleeding risk, and introduction of more potent antithrombotic medications in combination with regional anesthesia has resulted in a need for more than “consensus statements” to safely manage regional interventions during anticoagulant/thromboprophylactic therapy. PMID:26347411

  8. Antiplatelet and anticoagulant effects of diterpenes isolated from the marine alga, Dictyota menstrualis.

    PubMed

    de Andrade Moura, Laura; Marqui de Almeida, Ana Carolina; Domingos, Thaisa Francielle Souza; Ortiz-Ramirez, Fredy; Cavalcanti, Diana Negrão; Teixeira, Valéria Laneuville; Fuly, André Lopes

    2014-05-01

    Cardiovascular diseases represent a major cause of disability and death worldwide. Therapeutics are available, but they often have unsatisfactory results and may produce side effects. Alternative treatments based on the use of natural products have been extensively investigated, because of their low toxicity and side effects. Marine organisms are prime candidates for such products, as they are sources of numerous and complex substances with ecological and pharmacological effects. In this work, we investigated, through in vitro experiments, the effects of three diterpenes (pachydictyol A, isopachydictyol A and dichotomanol) from the Brazilian marine alga, Dictyota menstrualis, on platelet aggregation and plasma coagulation. Results showed that dichotomanol inhibited ADP- or collagen-induced aggregation of platelet-rich plasma (PRP), but failed to inhibit washed platelets (WP). In contrast, pachydictyol A and isopachydictyol A failed to inhibit the aggregation of PRP, but inhibited WP aggregation induced by collagen or thrombin. These diterpenes also inhibited coagulation analyzed by the prothrombin time and activated partial thromboplastin time and on commercial fibrinogen. Moreover, diterpenes inhibited the catalytic activity of thrombin. Theoretical studies using the Osiris Property Explorer software showed that diterpenes have low theoretical toxicity profiles and a drug-score similar to commercial anticoagulant drugs. In conclusion, these diterpenes are promising candidates for use in anticoagulant therapy, and this study also highlights the biotechnological potential of oceans and the importance of bioprospecting to develop medicines. PMID:24796305

  9. 21st century twist on Cullen's sign: new generation anticoagulants and splenic traum

    PubMed Central

    Bilkhu, Amarvir; Mosley, Frances; Gokhale, Jay A.

    2016-01-01

    New anticoagulants such as Rivaroxaban have become a popular choice for patients needing anticoagulation for atrial fibrillation or venous thromboembolism, chiefly because anticoagulation is maintained without the need for monitoring. This can be problematic in cases of trauma, and in this article, we discuss the management and outcome of managing an elderly patient with a shattered spleen while on Rivaroxaban. PMID:27511911

  10. Multinational development of a questionnaire assessing patient satisfaction with anticoagulant treatment: the 'Perception of Anticoagulant Treatment Questionnaire' (PACT-Q©)

    PubMed Central

    Prins, Martin H; Marrel, Alexia; Carita, Paulo; Anderson, David; Bousser, Marie-Germaine; Crijns, Harry; Consoli, Silla; Arnould, Benoit

    2009-01-01

    Background The side effects and burden of anticoagulant treatments may contribute to poor compliance and consequently to treatment failure. A specific questionnaire is necessary to assess patients' needs and their perceptions of anticoagulant treatment. Methods A conceptual model of expectation and satisfaction with anticoagulant treatment was designed by an advisory board and used to guide patient (n = 31) and clinician (n = 17) interviews in French, US English and Dutch. Patients had either atrial fibrillation (AF), deep venous thrombosis (DVT), or pulmonary embolism (PE). Following interviews, three PACT-Q language versions were developed simultaneously and further pilot-tested by 19 patients. Linguistic validations were performed for additional language versions. Results Initial concepts were developed to cover three areas of interest: 'Treatment', 'Disease and Complications' and 'Information about disease and anticoagulant treatment'. After clinician and patient interviews, concepts were further refined into four domains and 17 concepts; test versions of the PACT-Q were then created simultaneously in three languages, each containing 27 items grouped into four domains: "Treatment Expectations" (7 items), "Convenience" (11 items), "Burden of Disease and Treatment" (2 items) and "Anticoagulant Treatment Satisfaction" (7 items). No item was deleted or added after pilot testing as patients found the PACT-Q easy to understand and appropriate in length in all languages. The PACT-Q was divided into two parts: the first part to measure the expectations and the second to measure the convenience, burden and treatment satisfaction, for evaluation prior to and after anticoagulant treatment, respectively. Eleven additional language versions were linguistically validated. Conclusion The PACT-Q has been rigorously developed and linguistically validated. It is available in 14 languages for use with thromboembolic patients, including AF, PE and DVT patients. Its validation and

  11. Different models for oral anticoagulation management may be applied provided that minimal assistance criteria are fulfilled: an Italian experience.

    PubMed

    Prisco, Domenico; Antonucci, Emilia; Grifoni, Elisa; Mazzaglia, Giampiero; Bellandi, Tommaso; Tartaglia, Riccardo; Poli, Daniela

    2009-09-01

    The efficacy of adjusted-dose oral anticoagulant therapy (OAT) in the prevention of thrombotic complications in various clinical conditions is well documented. Management of OAT requires a trained physician, an organized system of follow-up, reliable international normalized ratio monitoring, and good patient communication and education. Drug interactions with coumarins are a major cause of excessive anticoagulation and hence could be an important determinant of bleeding in patients on OAT. An analysis conducted in Toscana in 2005 found 31,221 patients persistently on OAT. During the same period, potential drug-drug interactions were detected in 11,778 of these patients (37.7%). Thus, the regional government enacted a specific law for the organization of OAT management to give all patients a minimal standard of quality of OAT. A specific educational campaign was promoted with the slogan "Written is better." Three possible models to follow individual patients were identified in relation to available resources and geographic characteristics of the living area: Anticoagulation Clinic (AC), General Practitioner (GP), or combined AC and GP management. This experience, although obtained in a limited geographic area, could help improve the efficacy and safety of OAT management. PMID:19787561

  12. Lupus anticoagulant: a unique case with lupus anticoagulant and habitual abortion together with antifactor II antibody and bleeding tendency.

    PubMed

    Stormorken, H; Gjemdal, T; Bjøro, K

    1988-01-01

    Lupus anticoagulants (LA) are associated with various forms of thrombotic events. Of particular interest to obstetrics is the association with placental infarcts and habitual abortion. In the case described a near full-term viable infant was delivered subsequent to four early miscarriages. However, the mother had then developed an antifactor II antibody leading to grave hypoprothrombinemia with bleeding tendency, indicating efficient autoanticoagulation. This natural experiment indicates that these patients should receive anticoagulation during pregnancy, possibly in combination with steroids to depress the LA level. PMID:3139508

  13. Oral anticoagulants in coronary heart disease (Section IV). Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease.

    PubMed

    De Caterina, Raffaele; Husted, Steen; Wallentin, Lars; Andreotti, Felicita; Arnesen, Harald; Bachmann, Fedor; Baigent, Colin; Collet, Jean-Philippe; Halvorsen, Sigrun; Huber, Kurt; Jespersen, Jørgen; Kristensen, Steen Dalby; Lip, Gregory Y H; Morais, João; Rasmussen, Lars Hvilsted; Ricci, Fabrizio; Sibbing, Dirk; Siegbahn, Agneta; Storey, Robert F; Ten Berg, Jurriën; Verheugt, Freek W A; Weitz, Jeffrey I

    2016-04-01

    Until recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice. PMID:26952877

  14. Anticoagulation during pregnancy in patients with a prosthetic heart valve.

    PubMed

    Castellano, Jose M; Narayan, Rajeev L; Vaishnava, Prashant; Fuster, Valentin

    2012-07-01

    Effective anticoagulation is mandatory for pregnant women with mechanical heart valves. Oral anticoagulants offer the best maternal protection against thrombosis, but their use might be associated with an appreciable risk of fetal malformations and pregnancy loss. By contrast, heparin derivatives are associated with a reduced risk of fetal damage, but an increased risk of valve thrombosis in the mother, even with appropriate dose adjustment and monitoring of therapeutic efficacy. Given the varying risks of available anticoagulation strategies, and the paucity of data to inform the optimal approach, no single accepted treatment option exists for pregnant women with mechanical prosthetic valves. Although low-molecular-weight heparin is considered more efficacious than unfractionated heparin, treatment failures, even at therapeutic levels of factor Xa inhibition, have been reported. The risk of warfarin-related embryopathy might be overstated, particularly at doses ≤ 5 mg daily. We advocate an individualized anticoagulation strategy that takes into account the patient's preferences, calls for the use of vitamin K antagonists throughout pregnancy (substituted with a heparin derivative only close to term) for those patients at the greatest risk of thromboembolism, and relies on close multidisciplinary collaboration between the cardiac and obstetric care teams. PMID:22584941

  15. Anticoagulant activity of some Artemisia dracunculus leaf extracts

    PubMed Central

    Duric, Kemal; Kovac-Besovic, Elvira E.; Niksic, Haris; Muratovic, Samija; Sofic, Emin

    2015-01-01

    Platelet hyperactivity and platelet interaction with endothelial cells contribute to the development and progression of many cardiovascular diseases such as atherosclerosis and thrombosis. The impact of platelet activity with different pharmacological agents, such as acetylsalicylic acid and coumarin derivatives, has been shown to be effective in the prevention of cardiovascular disease. Artemisia dracunculus, L. Asteraceae (Tarragon) is used for centuries in the daily diet in many Middle Eastern countries, and it is well known for its anticoagulant activity. The present study investigates the presence of coumarins in tarragon leaves and subsequently determines the extract with a major amount of coumarin derivatives. The solvents of different polarities and different pH values were used for the purpose of purifying the primary extract in order to obtain fractions with the highest coumarin content. Those extracts and fractions were investigated for their anticoagulant activity by determining prothrombin time (PT) and the international normalized ratio (INR), expressed in relation to the coagulation time of the healthy person. Purified extracts and fractions obtained from plant residue after essential oil distillation, concentrated in coumarin derivatives, showed the best anticoagulant activity, using samples of human blood. INR maximum value (2.34) and consequently the best anticoagulant activity showed the methanol extract at concentration of 5%. The INR value of normal plasma in testing this extract was 1.05. PMID:26042507

  16. Coumarin derivatives from Ainsliaea fragrans and their anticoagulant activity

    PubMed Central

    Lei, Liang; Xue, Yong-bo; Liu, Zhong; Peng, Si-si; He, Yan; Zhang, Yang; Fang, Rong; Wang, Jian-ping; Luo, Zeng-wei; Yao, Guang-min; Zhang, Jin-wen; Zhang, Geng; Song, Hong-ping; Zhang, Yong-hui

    2015-01-01

    Coumarin derivatives are an important class of C6–C3 plant metabolites that show a variety of bioactivities. Currently, most clinical anticoagulant agents are coumarins, such as warfarin, dicoumarol and acenocoumarol, and patients taking these drugs must be monitored for adverse reactions. In a search for safe and effective anticoagulant compounds from Chinese herbal medicine, a screening procedure on the whole plant of Ainsliaea fragrans was performed. The phytochemical investigation of this plant afforded five new coumarin derivatives, including a pair of natural 4-hydroxycoumarin enantiomers (1), a pair of coumarin enantiomers with a rare polycyclic pyrano[3-2c] carbon skeleton (2) and a 7-hydroxycoumarin derivative (3), together with 5 known biogenetically related compounds (4–8). Enantioseparation of 1 and 2 produced optically pure compounds 1a, 1b, 2a and 2b. The absolute configurations of the new compounds were confirmed by single-crystal X-ray diffraction analysis. In addition, we evaluated the anticoagulant activity of all isolates via activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) assays in vitro and in vivo. Of note, compound 3 displayed potent anticoagulant activity and no significant hepatic or renal toxicity, which could make it a promising agent for further preclinical evaluation for preventing abnormal blood clotting. PMID:26315062

  17. Anticoagulant activity of some Artemisia dracunculus leaf extracts.

    PubMed

    Durić, Kemal; Kovac Besovic, Elvira E; Niksic, Haris; Muratovic, Samija; Sofic, Emin

    2015-01-01

    Platelet hyperactivity and platelet interaction with endothelial cells contribute to the development and progression of many cardiovascular diseases such as atherosclerosis and thrombosis. The impact of platelet activity with different pharmacological agents, such as acetylsalicylic acid and coumarin derivatives, has been shown to be effective in the prevention of cardiovascular disease. Artemisia dracunculus, L. Asteraceae (Tarragon) is used for centuries in the daily diet in many Middle Eastern countries, and it is well known for its anticoagulant activity. The present study investigates the presence of coumarins in tarragon leaves and subsequently determines the extract with a major amount of coumarin derivatives. The solvents of different polarities and different pH values were used for the purpose of purifying the primary extract in order to obtain fractions with the highest coumarin content. Those extracts and fractions were investigated for their anticoagulant activity by determining prothrombin time (PT) and the international normalized ratio (INR), expressed in relation to the coagulation time of the healthy person. Purified extracts and fractions obtained from plant residue after essential oil distillation, concentrated in coumarin derivatives, showed the best anticoagulant activity, using samples of human blood. INR maximum value (2.34) and consequently the best anticoagulant activity showed the methanol extract at concentration of 5%.  The INR value of normal plasma in testing this extract was 1.05. PMID:26042507

  18. Anticoagulants used in plasma collection affect adipokine multiplexed measurements.

    PubMed

    Allione, Alessandra; Di Gaetano, Cornelia; Dani, Nadia; Barberio, Davide; Sieri, Sabina; Krogh, Vittorio; Matullo, Giuseppe

    2016-04-01

    Obesity is an important health problem worldwide. Adipose tissue acts as an endocrine organ that secretes various bioactive substances, called adipokines, including pro-inflammatory biomarkers such as TNF-α, IL-6, leptin and C-reactive protein (CRP) and anti-inflammatory molecules such as adiponectin. The deregulated production of adipokines in obesity is linked to the pathogenesis of various disease processes and monitoring their variation is critical to understand metabolic diseases. The aim of this study was to determine the plasma concentration of adipokines in healthy subjects by multiplexed measurements and the effect of anticoagulants on their levels. Plasma samples from 10 healthy donors were collected in two different anticoagulants (sodium citrate or heparin). All markers, excluding TNF-α, showed significantly higher concentrations in heparinized compared to citrate plasma. However, levels of adipokines in different plasma samples were highly correlated for most of these markers. We reported that different anticoagulants used in the preparation of the plasma samples affected the measurements of some adipokines. The importance of the present results in epidemiology is relevant when comparing different studies in which blood samples were collected with different anticoagulants. PMID:26945995

  19. Qualitative identification of rodenticide anticoagulants by LC-MS/MS.

    PubMed

    Middleberg, Robert A; Homan, Joseph

    2012-01-01

    Rodenticide anticoagulants are used in the control of rodent populations. In addition to accidental ingestions in humans, such agents have also been used for homicidal and suicidal purposes. There are two major groups of rodenticide anticoagulants - hydroxycoumarins and indanediones. Before the advent of LC-MS/MS, analysis for such agents was relegated to such techniques as TLC and HPLC with nonspecific modes of detection. LC-MS/MS has been used to determine any given number of rodenticide anticoagulants in animal tissues, foods, plasma, etc. Use of this technique allows for the simultaneous identification of individual compounds within both classes of rodenticide anticoagulants. The LC-MS/MS method presented allows for simultaneous qualitative identification of brodifacoum, bromadiolone, chlorphacinone, dicumarol, difenacoum, diphacinone, and warfarin in blood, serum, and plasma using ESI in the negative mode. Two transitions are monitored for each analyte after a simple sample preparation. Chromatographic separation is accomplished using a gradient of ammonium hydroxide in water and ammonium hydroxide in methanol. Chloro-warfarin is used as internal standard. PMID:22767114

  20. Can the anticoagulant effects of dabigatran be reversed?

    PubMed

    Bickley, Aida Rebecca; Wallace, Caleb

    2016-09-01

    Idarucizumab is a humanized monoclonal antibody fragment for reversal of the anticoagulant effects of dabigatran. This drug can be used for patients who need emergency surgery or invasive procedures, as well as those with life-threatening or uncontrolled bleeding. PMID:27575900

  1. Perioperative anticoagulation for children with prosthetic mechanical valves.

    PubMed

    Rees, P; Grech, V

    2000-04-01

    The insertion of a mechanical heart valve predisposes to thrombosis and embolism, and for this reason, individuals with mechanical valves who undergo dental/surgical procedures must take special precautions. In this article, we illustrate a protocol for anticoagulation during such procedures in individuals with mechanical valves. PMID:22368581

  2. Peribulbar anesthesia in 750 patients treated with oral anticoagulants

    PubMed Central

    Calenda, Emile; Genevois, Olivier; Cardon, Annie; Muraine, Marc

    2014-01-01

    AIM To check the safety of continuation of oral anticoagulants in ophthalmic procedures requiring a peribulbar anesthesia. METHOD A prospective case control study included 750 patients with oral anticoagulants in group A and 750 patients who had never been treated with oral anticoagulant in group B. Hemorrhages were graded as follows: 1) spot ecchymosis of eyelid and or subconjunctival hemorrhage; 2) eyelid ecchymosis involving half of the lid surface area; 3) eyelid ecchymosis all around the eye, no increase in intraocular pressure; 4) retrobulbar hemorrhage with increased intraocular pressure. RESULTS In group A, grade 1 was observed in 13 patients (1.74%) and grade 2 in 2 patients (0.26%). In group B, grade 1 was observed in 12 patients (1.6%) and grade 2 was absent. No 3 or 4 hemorrhage grade was encountered in both groups. There was not significant difference in grade 1 hemorrhage between both groups (P=0.21). CONCLUSION Oral anticoagulants were not associated with a significant increase in potentially sight-threatening local anesthetic complications. PMID:24634874

  3. Adverse Outcomes of Anticoagulant Use among Hospitalized Patients with Chronic Kidney Disease: A Comparison of the Rates of Major Bleeding Events between Unfractionated Heparin and Enoxaparin

    PubMed Central

    Saheb Sharif-Askari, Fatemeh; Syed Sulaiman, Syed Azhar; Saheb Sharif-Askari, Narjes; Al Sayed Hussain, Ali; Railey, Mohammad Jaffar

    2014-01-01

    Background Anticoagulation therapy is usually required in patients with chronic kidney disease (CKD) for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding. Objectives To determine the incidence of adverse outcomes of anticoagulants in hospitalized patients with CKD, and to compare the rates of major bleeding events between the unfractionated heparin (UFH) and enoxaparin users. Methods One year prospective observational study was conducted in patients with CKD stages 3 to 5 (estimated GFR, 10–59 ml/min/1.73 m2) who were admitted to the renal unit of Dubai Hospital. Propensity scores for the use of anticoagulants, estimated for each of the 488 patients, were used to identify a cohort of 117 pairs of patients. Cox regression method was used to estimate association between anticoagulant use and adverse outcomes. Results Major bleeding occurred in 1 in 3 patients who received anticoagulation during hospitalization (hazard ratio [HR], 4.61 [95% confidence interval [CI], 2.05–10.35]). Compared with enoxaparin users, patients who received anticoagulation with unfractionated heparin had a lower mean [SD] serum level of platelet counts (139.95 [113]×103/µL vs 205.56 [123] ×103/µL; P<0.001), and had a higher risk of major bleeding (HR, 4.79 [95% CI, 1.85–12.36]). Furthermore, compared with those who did not receive anticoagulants, patients who did had a higher in-hospital mortality (HR, 2.54 [95% CI, 1.03–6.25]); longer length of hospitalization (HR, 1.04 [95% CI, 1.01–1.06]); and higher hospital readmission at 30 days (HR, 1.79 [95% CI, 1.10–2.91]). Conclusions Anticoagulation among hospitalized patients with CKD was significantly associated with an increased risk of bleeding and in-hospital mortality. Hence, intensive monitoring and preventive measures such as laboratory monitoring and/or dose adjustment are warranted. PMID:25181525

  4. Limited evidence on persistence with anticoagulants, and its effect on the risk of recurrence of venous thromboembolism: a systematic review of observational studies

    PubMed Central

    Vora, Pareen; Soriano-Gabarró, Montse; Suzart, Kiliana; Persson Brobert, Gunnar

    2016-01-01

    Purpose The risk of venous thromboembolism (VTE) recurrence is high following an initial VTE event, and it persists over time. This recurrence risk decreases rapidly after starting with anticoagulation treatment and reduces by ~80%–90% with prolonged anticoagulation. Nonpersistence with anticoagulants could lead to increased risk of VTE recurrence. This systematic review aimed to estimate persistence at 3, 6, and 12 months with anticoagulants in patients with VTE, and to evaluate the risk of VTE recurrence in nonpersistent patients. Methods PubMed and Embase® were searched up to May 3, 2014 and the search results updated to May 31, 2015. Studies involving patients with VTE aged ≥18 years, treatment with anticoagulants intended for at least 3 months or more, and reporting data for persistence were included. Proportions were transformed using Freeman–Tukey double arcsine transformation and pooled using the DerSimonian–Laird random-effects approach. Results In total, 12 observational studies (7/12 conference abstracts) were included in the review. All 12 studies either reported or provided data for persistence. The total number of patients meta-analyzed to estimate persistence at 3, 6, and 12 months was 71,969 patients, 58,940 patients, and 68,235 patients, respectively. The estimated persistence for 3, 6, and 12 months of therapy was 83% (95% confidence interval [CI], 78–87; I2=99.3%), 62% (95% CI, 58–66; I2=98.1%), and 31% (95% CI, 22–40; I2=99.8%), respectively. Only two studies reported the risk of VTE recurrence based on nonpersistence – one at 3 months and the other at 12 months. Conclusion Limited evidence showed that persistence was suboptimal with an estimated 17% patients being nonpersistent with anticoagulants in the crucial first 3 months. Persistence declined over 6 and 12 months. Observational data on persistence with anticoagulation treatment, especially direct oral anticoagulants, in patients with VTE and its effect on risk of VTE

  5. Novel Oral Anticoagulant Use Among Patients with Atrial Fibrillation Hospitalized with Ischemic Stroke or Transient Ischemic Attack

    PubMed Central

    Patel, Priyesh A.; Zhao, Xin; Fonarow, Gregg C.; Lytle, Barbara L.; Smith, Eric E.; Xian, Ying; Bhatt, Deepak L.; Peterson, Eric D.; Schwamm, Lee H.; Hernandez, Adrian F.

    2015-01-01

    Background Novel oral anticoagulants (NOACs) have been shown to be at least as good as warfarin for preventing stroke or transient ischemic attack (TIA) in patients with atrial fibrillation (AF), yet diffusion of these therapies and patterns of use among AF patients with ischemic stroke and TIA have not been well characterized. Methods and Results Using data from Get With The Guidelines®–Stroke, we identified a cohort of 61,655 AF patients with ischemic stroke or TIA hospitalized between 10/2010–09/2012 and discharged on warfarin or NOAC (either dabigatran or rivaroxaban). Multivariable logistic regression was used to identify factors associated with NOAC versus warfarin therapy. In our study population, warfarin was prescribed to 88.9%, dabigatran to 9.6%, and rivaroxaban to 1.5%. NOAC use increased from 0.04% to a 16–17% plateau during the study period, though anticoagulation rates among eligible patients did not change appreciably (93.7% vs. 94.1% from first quarter 2011 to second quarter 2012), suggesting a trend of switching from warfarin to NOACs rather than increased rates of anticoagulation among eligible patients. Several bleeding risk factors and CHA2DS2-VASc scores were lower among those discharged on NOAC versus warfarin therapy (47.9% vs. 40.9% with CHA2DS2-VASc ≤5, p<0.001 for difference in CHA2DS2-VASc). Conclusions NOACs have had modest but growing uptake over time among AF patients hospitalized with stroke or TIA and are prescribed to patients with lower stroke risk compared to warfarin. PMID:26058721

  6. Interrupting Anticoagulation in Patients With Nonvalvular Atrial Fibrillation

    PubMed Central

    Yates, Scott W.

    2014-01-01

    Three target-specific oral anticoagulants (TSOACs)—dabigatran, rivaroxaban, and apixaban—have been approved by the FDA to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; however, no agents are currently approved to reverse the anticoagulant effects of these TSOACs in cases of active bleeding. This review discusses the benefits and risks of these TSOACs from a clinician’s perspective, with a focus on the interruption of treatment for either elective or emergent surgery, monitoring, and reversal of anticoagulation. Available coagulation assays are not ideal for monitoring the effects of TSOACs and do not provide reliable quantitative measurement of their anticoagulant effects. When necessary, activated partial thromboplastin time (aPTT) may provide qualitative information on dabigatran, and prothrombin time (PT) may provide qualitative assessment of the presence of the factor Xa inhibitors, rivaroxaban and apixaban. Current recommendations for reversal of TSOACs are based largely on limited and sometimes conflicting data from in vitro or in vivo animal models, and clinical experience with these recommendations is also limited. Methods that have been investigated for effectiveness for reversal of the pharmacodynamic effects of the TSOACs include dialysis, activated charcoal, prothrombin complex concentrate (PCC), and recombinant activated factor VII. It is important to note that even within a class of anticoagulant drugs, compounds respond differently to reversal agents; therefore, recommendations for one agent should not be extrapolated to another, even if they are from the same therapeutic class. New antidotes are being explored, including a mouse monoclonal antibody to dabigatran; andexanet alfa, a potential universal factor Xa inhibitor reversal agent; and a synthetic small molecule (PER977) that may be effective for the reversal of factor Xa inhibitors and direct thrombin inhibitors. Given the short half

  7. Anticoagulant-induced pseudothrombocytopenia occurring after transcatheter arterial embolization for hepatocellular carcinoma.

    PubMed

    Yoshikawa, Takeshi; Nakanishi, Kayo; Maruta, Tsutomu; Takenaka, Daisuke; Hirota, Shozo; Matsumoto, Shinichi; Saigo, Katsuyasu; Ohno, Yoshiharu; Fujii, Masahiko; Sugimura, Kazuro

    2006-08-01

    Pseudothrombocytopenia (PTCP) is the in vitro phenomenon of anticoagulant-activated platelet agglutination that results in spuriously low platelet counts. We report the case of a 65-year-old man with EDTA- and sodium citrate-dependent PTCP occurring after transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) due to hepatitis C cirrhosis. Invasion of the portal and hepatic veins by HCC formed severe trans-tumoral arterio-venous shunts that were effectively treated by TAE. Two days after the therapy, PTCP was seen on blood count and continued for 4 months. The patient received unnecessary treatment for disseminated intravascular coagulation (DIC) until the diagnosis of PTCP was established. PTCP is a rare complication but should be considered after TAE for HCC; lack of recognition may lead the physician to misdiagnosis and patient mismanagement. PMID:16793782

  8. Low anticoagulant heparin disrupts Plasmodium falciparum rosettes in fresh clinical isolates.

    PubMed

    Leitgeb, Anna M; Blomqvist, Karin; Cho-Ngwa, Fidelis; Samje, Moses; Nde, Peter; Titanji, Vincent; Wahlgren, Mats

    2011-03-01

    The binding of Plasmodium falciparum parasitized erythrocytes to uninfected erythrocytes (rosetting) is associated with severe malaria. The glycosaminoglycan heparan sulfate is an important receptor for rosetting. The related glycosaminoglycan heparin was previously used in treatment of severe malaria, although abandoned because of the occurrence of severe bleedings. Instead, low anticoagulant heparin (LAH) has been suggested for treatment. LAH has successfully been evaluated in safety studies and found to disrupt rosettes and cytoadherence in vitro and in vivo in animal models, but the effect of LAH on fresh parasite isolates has not been studied. Herein, we report that two different LAHs (DFX232 and Sevuparin) disrupt rosettes in the majority of fresh isolates from Cameroonian children with malaria. The rosette disruption effect was more pronounced in isolates from complicated cases than from mild cases. The data support LAH as adjunct therapy in severe malaria. PMID:21363975

  9. Low Anticoagulant Heparin Disrupts Plasmodium falciparum Rosettes in Fresh Clinical Isolates

    PubMed Central

    Leitgeb, Anna M.; Blomqvist, Karin; Cho-Ngwa, Fidelis; Samje, Moses; Nde, Peter; Titanji, Vincent; Wahlgren, Mats

    2011-01-01

    The binding of Plasmodium falciparum parasitized erythrocytes to uninfected erythrocytes (rosetting) is associated with severe malaria. The glycosaminoglycan heparan sulfate is an important receptor for rosetting. The related glycosaminoglycan heparin was previously used in treatment of severe malaria, although abandoned because of the occurrence of severe bleedings. Instead, low anticoagulant heparin (LAH) has been suggested for treatment. LAH has successfully been evaluated in safety studies and found to disrupt rosettes and cytoadherence in vitro and in vivo in animal models, but the effect of LAH on fresh parasite isolates has not been studied. Herein, we report that two different LAHs (DFX232 and Sevuparin) disrupt rosettes in the majority of fresh isolates from Cameroonian children with malaria. The rosette disruption effect was more pronounced in isolates from complicated cases than from mild cases. The data support LAH as adjunct therapy in severe malaria. PMID:21363975

  10. Results with an anticoagulation protocol in 99 SynCardia total artificial heart recipients.

    PubMed

    Copeland, Jack; Copeland, Hannah; Nolan, Paul; Gustafson, Monica; Slepian, Marvin; Smith, Richard

    2013-01-01

    For 15 years, we employed a consistent anticoagulation protocol in 99 consecutive SynCardia Systems total artificial heart (TAH) recipients. Thromboelastography and platelet aggregation studies were used for evaluating and modulating therapy with dipyridamole, pentoxiphylline, aspirin, and heparin. Partial thromboplastin times, international normalized ratios, and platelet counts were also followed. After the second post-implant day in patients who were free of endo-device infection (97 patients), the embolic stroke incidence was 0.08 per patient year. This included 23.6 patient years of device support. There were no spontaneous hemorrhagic strokes. Two patients had endo-device infections and both had strokes. Postimplantation bleeding was seen in 20% of patients. All but two of these were within the first postoperative week. In all, 4% of patients had gastrointestinal bleeding. We did not observe heparin-induced thrombocytopenia in any patient. We conclude that stroke rates on TAH support have been low, and recommend this protocol. PMID:23644607

  11. [Anticoagulation and platelet inhibition - dosing recommendations at the beginning and the end of treatment].

    PubMed

    Ivandic, Boris T; Zankl, Alexandra; Katus, Hugo A

    2008-10-01

    Anticoagulants and anti-platelet drugs are essential and widely used therapeutic tools in modern cardiovascular medicine. However, the initiation of anti-thrombotic therapies, their termination, or transient discontinuation (e.g. for surgical procedures) are critical steps which have to be managed appropriately. In the near future, several novel irreversibly or reversibly acting anti-thrombotic drugs with direct and indirect mechanisms of action, will be approved. Their prescription will require a deep understanding of their pharmacodynamics and -kinetics. In addition, pharmacogenomic issues will become increasingly important for the optimization of individual therapeutic strategies. This review summarizes clinically relevant principles and discusses them in the light of the assessment of the individual thrombotic and bleeding risks. PMID:18821519

  12. [Anticoagulant treatment of patients with atrial fibrillations: dependent on age and other risk factors for thromboembolism].

    PubMed

    Vink, R; van den Brink, R B A; Levi, M

    2002-11-30

    Atrial fibrillation is a common arrhythmic disorder which is becoming increasingly prevalent among the elderly. Atrial fibrillation is an independent risk factor for ischaemic stroke. Patients with hypertension, heart failure, diabetes, age older than 65 years, previous thromboembolisms, left atrial enlargement and left ventricular dysfunction have an increased risk. Coumarins (with a target international normalised ratio (INR) of 2.0 to 3.0) are the treatment of first choice in patients with atrial fibrillation. In young patients without additional risk factors, acetyl salicylic acid provides sufficient protection. The management of anticoagulant therapy during electric cardioversion in the acute phase of an ischaemic stroke and during elective surgical interventions, is still a subject of clinical research. PMID:12497755

  13. Anticoagulants and Statins As Pharmacological Agents in Free Flap Surgery: Current Rationale

    PubMed Central

    Pršić, Adnan; Kiwanuka, Elizabeth; Caterson, Stephanie A.

    2015-01-01

    Microvascular free flaps are key components of reconstructive surgery, but despite their common use and usual reliability, flap failures still occur. Many pharmacological agents have been utilized to minimize risk of flap failure caused by thrombosis. However, the challenge of most antithrombotic therapy lies in providing patients with optimal antithrombotic prophylaxis without adverse bleeding effects. There is a limited but growing body of evidence suggesting that the vasoprotective and anti-inflammatory actions of statins can be beneficial for free flap survival. By inhibiting mevalonic acid, the downstream effects of statins include reduction of inflammation, reduced thrombogenicity, and improved vasodilation. This review provides a summary of the pathophysiology of thrombus formation and the current evidence of anticoagulation practices with aspirin, heparin, and dextran. In addition, the potential benefits of statins in the perioperative management of free flaps are highlighted. PMID:26617953

  14. Postpartum dilated cardiomyopathy in a patient with systemic lupus erythematosus, nephritis and lupus anticoagulant: a diagnostic dilemma

    PubMed Central

    Hall, Daniel; New, David; Kelly, Teresa

    2011-01-01

    A 32-year-old Caucasian woman presented with shortness of breath four weeks postpartum. She was known to suffer from systemic lupus erythematosus with cutaneous, joint and minor renal involvement. During pregnancy, the patient had developed nephrotic syndrome for which she was managed with prophylactic anticoagulation and corticosteroid therapy. A leg deep vein thrombosis had arisen following caesarean section following antepartum haemorrhage. Examination revealed a heart murmur, and pulmonary signs. Computed tomography pulmonary angiogram showed cardiomegaly and bilateral pleural effusions but no pulmonary embolus. Echocardiogram demonstrated dilated cardiomyopathy. An initial diagnosis of peripartum cardiomyopathy was considered, with lupus myocarditis and coronary in situ thrombosis among the differential diagnoses.

  15. Factor XI as a target for antithrombotic therapy

    PubMed Central

    Bane, Charles E.; Gailani, David

    2014-01-01

    Anticoagulants currently used in clinical practice to treat thromboembolic disorders are effective but increase the risk of severe bleeding because they target proteins that are essential for normal coagulation (hemostasis). Drugs with better safety profiles are required for prevention and treatment of thromboembolic disease. Coagulation factor XIa has emerged as a novel target for safer anticoagulant therapy because of its role in thrombosis and its relatively small contribution to hemostasis. PMID:24886766

  16. Cognitive function and adherence to anticoagulation treatment in patients with atrial fibrillation

    PubMed Central

    Jankowska-Polańska, Beata; Katarzyna, Lomper; Lidia, Alberska; Joanna, Jaroch; Dudek, Krzysztof; Izabella, Uchmanowicz

    2016-01-01

    Background Medication adherence is an integral part of the comprehensive care of patients with atrial fibrillation (AF) receiving oral anticoagulations (OACs) therapy. Many patients with AF are elderly and may suffer from some form of cognitive impairment. This study was conducted to investigate whether cognitive impairment affects the level of adherence to anticoagulation treatment in AF patients. Methods The study involved 111 AF patients (mean age, 73.5 ± 8.3 years) treated with OACs. Cognitive function was assessed using the Mini Mental State Examination (MMSE). The level of adherence was assessed by the 8-item Morisky Medication Adherence Scale (MMAS-8). Scores on the MMAS-8 range from 0 to 8, with scores < 6 reflecting low adherence, 6 to < 8 medium adherence, and 8 high adherence. Results 46.9% of AF patients had low adherence, 18.8% had moderate adherence, and 33.3% had high adherence to OACs. Patients with lower adherence were older than those with moderate or high adherence (76.6 ± 8.7 vs. 71.3 ± 6.4 vs. 71.1 ± 6.7 years) and obtained low MMSE scores, indicating cognitive disorders or dementia (MMSE = 22.3 ± 4.2). Patients with moderate or high adherence obtained high MMSE test results (27.5 ± 1.7 and 27.5 ± 3.6). According to Spearman's rank correlation, worse adherence to treatment with OACs was determined by older age (rS = −0.372) and lower MMSE scores (rS = 0.717). According to multivariate regression analysis, the level of cognitive function was a significant independent predictor of adherence (b = 1.139). Conclusions Cognitive impairment is an independent determinant of compliance with pharmacological therapy in elderly patients with AF. Lower adherence, beyond the assessment of cognitive function, is related to the age of patients. PMID:27605935

  17. Which is the best anticoagulant for whole blood aggregometry platelet function testing? Comparison of six anticoagulants and diverse storage conditions.

    PubMed

    Kaiser, Andreas Friedrich Christoph; Neubauer, Horst; Franken, Cora Christina; Krüger, Jan-Christoph; Mügge, Andreas; Meves, Saskia Hannah

    2012-01-01

    Major hindrances of impedance aggregometry are caused by limited storage time and the requirement of ex vivo anticoagulation. Data on the influence of different anticoagulants and storage conditions are rare and incomplete. This study has systematically examined the influence of six different anticoagulants (sodium and lithium heparin, 20 µg/mL and 45 µg/mL r-hirudin, benzylsulfonyl-D-Arg-Pro-4-amidinobenzylamide (BAPA), and citrate) on the results of Adenosine 5'-diphosphate (ADP) and arachidonic acid (AA) induced measurements using multiple-electrode impedance aggregometer (MEA). Measurements were carried out in a time frame of 0 min up to 48 h after blood withdrawal. In addition, the influence of storage temperatures of 4°C and 37°C was evaluated. Results of ADP-induced tests significantly varied within the first 30 min in all tested anticoagulants, in citrated blood even within the first 60 min. They remained stable up to 2 h in 20 µg/mL r-hirudin and BAPA, 4 h in citrate, 8 h in 45 µg/mL r-hirudin, and lithium heparin and up to a maximum of 12 h in sodium heparin anticoagulated blood. The analysis of AA-induced tests revealed no significantly different results up to 6 h when BAPA was used, 8 h in lithium heparin, 20 µg/mL r-hirudin and citrate, 12 h in 45 µg/mL r-hirudin, and even 24 h in sodium heparin-anticoagulated samples. A storage temperature of either 4°C or 37°C in contrast to room temperature had a negative influence on the stability of results. In conclusion, sodium heparin and 45 µg/mL r-hirudin as anticoagulants guarantee the longest storage time for impedance aggregometry. PMID:21999185

  18. [Quality of life of elderly people on oral anticoagulant for atrial fibrillation: VKA versus direct oral anticoagulants].

    PubMed

    Fareau, Sarah; Baumstarck, Karine; Farcet, Anaïs; Molines, Catherine; Auquier, Pascal; Retornaz, Frédérique

    2015-03-01

    Atrial fibrillation (AF) is the most common arrhythmia. Its prevalence increases with age and increases the risk of stroke and systemic embolism. Few data are currently available on the quality of life (QOL) of anticoagulated patients with the advent of direct oral anticoagulants (DOAC). Our study aims to describe levels of QOL in elderly patients with AF receiving oral anticoagulants and compare QOL of patients treated with vitamin K antagonists (VKA) and DOAC. This prospective study included patients of 65 years and over, receiving anticoagulants for AF (VKA or DOAC) from general practice (n=70) or cardiac practice (n=30). The patients completed a self-administered questionnaire that included demographic, geriatric data and a QOL standardized scale: the anti-clot treatment scale (ACTS) 17 items exploring two dimensions "Burdens" and "Benefits". Eighty-nine patients were enrolled: 61 were taking VKA and 28 taking DOAC. Our two groups were comparable for all demographic and clinical characteristics studied. Our patients' mean scores were 48.6±12.1 on Burdens and 9.7±3.8 on Benefits. Burdens and Benefits scores were significantly better for patients treated with DOAC compared to patients with VKA (p<0.0001 and p<0.01, respectively). Anticoagulation in the elderly should be encouraged given the high thrombotic risk of AF. No matter what kind of molecule is chosen if in accordance to good guidance. Patients treated with ACOD seem to have a better QOL, but these results should be confirmed through larger randomized studies. PMID:25786423

  19. Pulmonary embolism--the role of thrombolytic therapy in its management.

    PubMed Central

    More, R. S.; Chauhan, A.

    1996-01-01

    In massive pulmonary embolism where there may be evidence of right ventricular dysfunction and acute pulmonary hypertension, anticoagulation therapy alone may prove inadequate. In such situations use of thrombolytic agents produces an improvement in haemodynamics compared to anticoagulants alone, although studies to date have been too small to address the issue of mortality benefit. It would appear that all age groups gain benefit from the use of thrombolytics. Studies that have compared thrombolytic agents and anticoagulants are discussed. In addition, the issues of the choice of thrombolytic agent and the different modes of delivery of therapy are addressed. Images Figure PMID:8731706

  20. Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism.

    PubMed

    Witt, Daniel M; Clark, Nathan P; Kaatz, Scott; Schnurr, Terri; Ansell, Jack E

    2016-01-01

    Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. The treatment of VTE is undergoing tremendous changes with the introduction of the new direct oral anticoagulants and clinicians need to understand new treatment paradigms. This article, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. Well-managed warfarin therapy remains an important anticoagulant option and it is hoped that anticoagulation providers will find the guidance contained in this article increases their ability to achieve optimal outcomes for their patients with VTE Pivotal practical questions pertaining to this topic were developed by consensus of the authors and were derived from evidence-based consensus statements whenever possible. The medical literature was reviewed and summarized using guidance statements that reflect the consensus opinion(s) of all authors and the endorsement of the Anticoagulation Forum's Board of Directors. In an effort to provide practical and implementable information about VTE and its treatment, guidance statements pertaining to choosing good candidates for warfarin therapy, warfarin initiation, optimizing warfarin control, invasive procedure management, excessive anticoagulation, subtherapeutic anticoagulation, drug interactions, switching between anticoagulants, and care transitions are provided. PMID:26780746

  1. Role of novel and emerging oral anticoagulants for secondary prevention of acute coronary syndromes.

    PubMed

    Ganetsky, Valerie S; Hadley, Diane E; Thomas, Tyan F

    2014-06-01

    Dual antiplatelet therapy has become a mainstay of long-term management of patients after an acute coronary syndrome (ACS). Mortality for these patients remains high despite current evidence-based treatment strategies. The coagulation cascade plays a role in the pathophysiology of ACS, and trials with warfarin in combination with dual antiplatelet therapy have found decreased rates of ischemic events at the expense of increased bleeding risk. Novel oral anticoagulants (NOACs) in the direct factor Xa (FXa) inhibitor and direct thrombin inhibitor (DTI) categories have been evaluated in combination with standard post-ACS therapy. Rivaroxaban, a FXa inhibitor, reduced the rates of ischemic events but increased major bleeding rates. Apixaban did not decrease the rates of ischemic events and also increased major bleeding rates. Other FXa inhibitors have not been studied in the long-term management of ACS (e.g., otamixaban), are not currently being studied in ongoing phase III trials (e.g., TAK-442), or have been discontinued by the manufacturer (e.g., darexaban). The DTI dabigatran had a 2- to 4-fold increased risk of major bleeding with unclear benefit for reducing ischemic events. The factor IXa inhibitor pegnivacogin is an RNA-based aptamer that has been studied in patients undergoing cardiac catheterization but has not been studied for long-term post-ACS management. The European Society of Cardiology Working Group on Thrombosis recommends the use of newer antiplatelet agents over addition of NOACs. Additional guidelines are available to guide management in patients requiring triple antithrombotic therapy but do not provide definitive recommendations on NOACs. Many questions remain about the place of NOACs for long-term post-ACS management. Recent trials have evaluated double versus triple antithrombotic therapy to balance efficacy and bleeding risk, but they did not include NOACs. It also remains unclear if NOACs hold a place in post-ACS therapy in the era of more

  2. Direct vitamin k antagonist anticoagulant treatment health care costs in patients with non-valvular atrial fibrillation

    PubMed Central

    2014-01-01

    Background There is evidence suggesting that most thromboembolic complications could be prevented with adequate pharmacological anticoagulation. We estimated the direct health care costs of anticoagulant treatment with oral vitamin K antagonists in patients diagnosed with non-valvular atrial fibrillation. Methods This observational study examined the clinical records of patients diagnosed with non-valvular atrial fibrillation who received anticoagulant treatment with oral vitamin K antagonists. Data from clinical records were used in the study: international normalized ratio, number of monitoring visits, type of anticoagulant, hospital admissions from complications, and concomitant medication. Drug cost was calculated based on the official Spanish Ministry of Health price list. Monitoring expenses were included the cost of the medical supplies used in the procedures. Hospitalization costs were calculated using the Diagnosis Related Group price for each case. Hospital visits costs were calculated by one of four different scenarios, using either the invoice rates for the regional health care authority or cost per visit as established by analytical accounting methods. Results We collected data from 1,257 patients diagnosed with non-valvular atrial fibrillation who were receiving oral anticoagulant therapy. Depending on the scheme used, the direct health care costs for these patients ranged from €423,695 - €1,436,038 per annum. The average cost per patient varied between €392 - €1,341, depending on the approach used. Patients with international normalized ratio values within the therapeutic range on 25% of their visits represented an average cost between €441.70 - €1,592. Those within the therapeutic range on 25%–50% of visits had associated costs of €512.37 - €1,703.91. When international normalized ratio values were within the therapeutic range on 50% - 75% of the visits, the costs ranged between €400.80- €1,375.74. The

  3. In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong

    2011-05-01

    Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.

  4. Contemporary Management of Atrial Fibrillation: Update on Anticoagulation and Invasive Management Strategies

    PubMed Central

    Crandall, Mark A.; Bradley, David J.; Packer, Douglas L.; Asirvatham, Samuel J.

    2009-01-01

    Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Its increasing prevalence, particularly among the elderly, renders it one of the most serious current medical epidemics. Several management questions confront the clinician treating a patient with AF: Should the condition be treated? Is the patient at risk of death or serious morbidity as a result of this diagnosis? If treatment is necessary, is rate control or rhythm control superior? Which patients need anticoagulation therapy, and for how long? This review of articles obtained by a search of the PubMed and MEDLINE databases presents the available evidence that can guide the clinician in answering these questions. After discussing the merits of available therapy, including medications aimed at controlling rate, rhythm, or both, we focus on the present status of ablative therapy for AF. Catheter ablation, particularly targeting the pulmonary veins, is being increasingly performed, although the precise indications for this approach and its effectiveness and safety are being actively investigated. We briefly discuss other invasive options that are less frequently used, such as pacemakers, defibrillators, left atrial appendage closure devices, and the surgical maze procedure. PMID:19567719

  5. Direct Oral Anticoagulants and Their Use in Treatment and Secondary Prevention of Acute Symptomatic Venous Thromboembolism.

    PubMed

    Granziera, Serena; Hasan, Arjumand; Cohen, Alexander Ander T

    2016-04-01

    Direct oral anticoagulants (DOACs) have been compared with standard therapy in large phase III studies to assess their safety and efficacy in the treatment of deep vein thrombosis and/or pulmonary embolism and in the secondary prevention of recurrent venous thromboembolism. Although the mean population age and the gross inclusion and exclusion criteria were similar across these studies, they differed in other aspects such as overall study design and acute treatment strategies. The 4 DOACs examined in phase III trials (apixaban, edoxaban, rivaroxaban, and dabigatran) showed noninferiority compared with standard therapy for the treatment of deep vein thrombosis and/or pulmonary embolism and for the prevention of recurrent venous thromboembolism. Furthermore, these DOACs exhibited a similar safety profile to standard therapy, with the risk of major bleeding significantly reduced in some of these studies. Rivaroxaban and apixaban were tested as a single-drug approach, whereas in the dabigatran and edoxaban studies, initial bridging with parenteral agents was employed. The purpose of this review is to compare the phase III studies of DOACs in this indication, to highlight the differences, and to discuss a series of clinically relevant issues, including the management of key patient subgroups (eg, fragile patients, those with cancer or renal impairment), extended treatment, use of comedications, heparin pretreatment versus a single-drug approach, and the bleeding profiles of the DOACs. PMID:26329910

  6. Interventional spine and pain procedures in patients on antiplatelet and anticoagulant medications: guidelines from the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and the World Institute of Pain.

    PubMed

    Narouze, Samer; Benzon, Honorio T; Provenzano, David A; Buvanendran, Asokumar; De Andres, José; Deer, Timothy R; Rauck, Richard; Huntoon, Marc A

    2015-01-01

    Interventional spine and pain procedures cover a far broader spectrum than those for regional anesthesia, reflecting diverse targets and goals. When surveyed, interventional pain and spine physicians attending the American Society of Regional Anesthesia and Pain Medicine (ASRA) 11th Annual Pain Medicine Meeting exhorted that existing ASRA guidelines for regional anesthesia in patients on antiplatelet and anticoagulant medications were insufficient for their needs. Those surveyed agreed that procedure-specific and patient-specific factors necessitated separate guidelines for pain and spine procedures. In response, ASRA formed a guidelines committee. After preliminary review of published complication reports and studies, committee members stratified interventional spine and pain procedures according to potential bleeding risk as low-, intermediate-, and high-risk procedures. The ASRA guidelines were deemed largely appropriate for the low- and intermediate-risk categories, but it was agreed that the high-risk targets required an intensive look at issues specific to patient safety and optimal outcomes in pain medicine. The latest evidence was sought through extensive database search strategies and the recommendations were evidence-based when available and pharmacology-driven otherwise. We could not provide strength and grading of these recommendations as there are not enough well-designed large studies concerning interventional pain procedures to support such grading. Although the guidelines could not always be based on randomized studies or on large numbers of patients from pooled databases, it is hoped that they will provide sound recommendations and the evidentiary basis for such recommendations. PMID:25899949

  7. Evaluation of anticoagulant activity of two algal polysaccharides.

    PubMed

    Faggio, C; Pagano, M; Dottore, A; Genovese, G; Morabito, M

    2016-09-01

    Marine algae are important sources of phycocolloids like agar, carrageenans and alginates used in industrial applications. Algal polysaccharides have emerged as an important class of bioactive products showing interesting properties. The aim of our study was to evaluate the potential uses as anticoagulant drugs of algal sulphate polysaccharides extracted from Ulva fasciata (Chlorophyta) and Agardhiella subulata (Rhodophyta) collected in Ganzirri Lake (Cape Peloro Lagoon, north-eastern Sicily, Italy). Toxicity of algal extracts through trypan blue test and anticoagulant action measured by activated partial thromboplastin time (APTT), prothrombin time (PT) test has been evaluated. Algal extracts showed to prolong the PT and APTT during the coagulation cascade and to avoid the blood coagulation of samples. Furthermore, the algal extracts lack toxic effects towards cellular metabolism and their productions are relatively at low cost. This permits to consider the algae as the biological source of the future. PMID:26360806

  8. New anticoagulant and antiplatelet agents: a primer for the gastroenterologist.

    PubMed

    Baron, Todd H; Kamath, Patrick S; McBane, Robert D

    2014-02-01

    A large number of patients worldwide receive anticoagulant and antiplatelet agents, collectively known as antithrombotic agents. Several new anticoagulants and antiplatelet agents recently were approved for use. Gastroenterologists may be unfamiliar with the mechanism of action, indications for use, and pharmacokinetics of these newer drugs. In patients undergoing elective and urgent endoscopic procedures, clinicians must be familiar with these medications to optimize outcomes. When the decision is made to continue the newer antithrombotic agents for elective procedures, the clinician must understand the risk that these agents may impart on procedural-induced bleeding. Finally, it is important to understand how to manage these agents in the presence of acute gastrointestinal bleeding. In this article the use of newer antithrombotic agents is reviewed. PMID:23735447

  9. Anticoagulant activity of Moon jellyfish (Aurelia aurita) tentacle extract.

    PubMed

    Rastogi, Akriti; Biswas, Sumit; Sarkar, Angshuman; Chakrabarty, Dibakar

    2012-10-01

    Moon jellyfish (Aurelia aurita) tentacle extract was studied for its anticoagulant activity in vitro. The Jellyfish Tentacle Extract (JFTE) showed very strong fibrinogenolytic activity by cleaving Aα and Bβ chain of fibrinogen molecule. The fibrinogenolytic activity was found to be stronger than some snake venom derived anticoagulants. JFTE also completely liquefied fibrin clots in 24 h. JFTE was found to contain both high and low molecular weight proteins/peptides. The fibrinogenolysis appears to be caused by high molecular weight fractions of the extract. It has been also noted that PMSF significantly reduced fibrinogenolytic activity and heating totally abolished it. Autolytic degradation of the high molecular weight protein was also noted. Autolysis slowed down, but did not abolish the fibrinogenolytic activity of the extract. PMID:22652129

  10. Predictors of recurrent venous thromboembolism and bleeding on anticoagulation.

    PubMed

    Menapace, Laurel A; McCrae, Keith R; Khorana, Alok A

    2016-04-01

    The impact of venous thromboembolism (VTE) in the cancer population remains substantial despite significant advances in detecting and treating thrombotic events. While there is extensive literature regarding predictors of first VTE event in cancer patients as well as a validated predictive score, less data exist regarding recurrent VTE in cancer cohorts and associated predictive variables. A similar paucity of data in regard to bleeding events in cancer patients receiving anticoagulation has been observed. This review article will highlight clinical risk factors as well as predictive biomarkers associated with recurrent VTE and bleeding in cancer patients receiving therapeutic anticoagulation. Predictive risk assessment models for cancer-associated recurrent VTE and bleeding are also discussed. PMID:27067987

  11. Emergent Bleeding in Patients Receiving Direct Oral Anticoagulants.

    PubMed

    Summers, Richard L; Sterling, Sarah A

    2016-01-01

    Direct oral anticoagulants (DOACs) offer clinical advantages over warfarin, such as minimal medication and food interactions and fixed dosing without the need for routine monitoring of coagulation status. As with all anticoagulants, bleeding, either spontaneous or provoked, is the most common complication. The long-term use of these drugs is increasing, and there is a crucial need for emergency medicine service professionals to understand the optimal management of associated bleeding. This review aims to describe the indications and pharmacokinetics of available DOACs; to discuss the risk of bleeding; to provide a treatment algorithm to manage DOAC-associated emergency bleeding; and to discuss future directions in bleeding management, including the role of specific reversal agents, such as the recently approved idarucizumab for reversal of the direct thrombin inhibitor dabigatran. Because air medical personnel are increasingly likely to encounter patients receiving DOACs, it is important that they have an understanding of how to manage patients with emergent bleeding. PMID:27255877

  12. The enhanced anticoagulation for graphene induced by COOH+ ion implantation

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoqi; Cao, Ye; Zhao, Mengli; Deng, Jianhua; Li, Xifei; Li, Dejun

    2015-01-01

    Graphene may have attractive properties for some biomedical applications, but its potential adverse biological effects, in particular, possible modulation when it comes in contact with blood, require further investigation. Little is known about the influence of exposure to COOH+-implanted graphene (COOH+/graphene) interacting with red blood cells and platelets. In this paper, COOH+/graphene was prepared by modified Hummers' method and implanted by COOH+ ions. The structure and surface chemical and physical properties of COOH+/graphene were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle measurement. Systematic evaluation of anticoagulation, including in vitro platelet adhesion assays and hemolytic assays, proved that COOH+/graphene has significant anticoagulation. In addition, at the dose of 5 × 1017 ions/cm2, COOH+/graphene responded best on platelet adhesion, aggregation, and platelet activation.

  13. [Use of direct oral anticoagulants in the elderly].

    PubMed

    Mickley, Frank; Geigenmüller, Grit; Schinköthe, Claudia

    2015-12-01

    Equal safety and efficacy of direct oral anticoagulants as compared to vitamin K antagonists have been shown in elderly and very old patients. The use of these seem to have certain advantages in this special patient cohort: higher drug safety, no need for lab monitoring, less drug-drug interactions and a lower rate of intracranial hemorrhages. However, more data is needed to quantify the exact bleeding risk for geriatric patients. Elderly patients suffer quite frequently from significant comorbidities, such as renal failure, dementia, vision loss etc., which might put them at higher risk to suffer from medication side effects, especially bleeding complications. Routine clinical examinations combined with monitoring of renal function are therefore of paramount importance. Regarding these precautions the use of the new oral anticoagulants in the elderly is hence quite justified and rising. PMID:26625228

  14. Drug Interactions of Direct-Acting Oral Anticoagulants.

    PubMed

    Fitzgerald, John Leonard; Howes, Laurence Guy

    2016-09-01

    In recent years, new direct-acting oral anticoagulants (DOACs) have been introduced into clinical practice that specifically inhibit either factor Ia or Xa. These drugs have, to a large extent, replaced warfarin for the treatment of venous thrombosis, pulmonary embolism, and non-valvular atrial fibrillation. They have potential advantages over warfarin in providing more stable anticoagulation and the lack of a need for regular venesection to monitor activity. They also have the promise of less drug and food interactions. All of these drugs are substrates for the permeability glycoprotein (P-gp) excretion system, and several are metabolised, in part, by cytochrome P450 (CYP) 3A4. This current article assesses the interactions that do or may occur with the DOACs, particularly with respect to the P-gp and CYP3A4 systems. PMID:27435452

  15. AParadigm Shift: The New Novel Oral Anticoagulation Agents.

    PubMed

    Saeed, Wajeeha; Burke, James F; Mirrani, Ghazi; Sirinivasa, Minisha; Nabi, Usman; Hayat, Umar; Khan, Zubair; Sardar, Muhammad Rizwan

    2016-07-01

    Atrial fibrillation (AF) is the most common arrhythmia and represents one-third of the arrhythmia-related hospital admissions in the developed countries. Embolic strokes associated with AF are more severe and disabling. Thromboembolic stroke prevention is a major goal in treatment of AF and Warfarin has successfully served this purpose for many years. Drug-drug interaction and regular monitoring with Warfarin pose a significant challenge where health care system has limited resources; and lack of a well-structured health system, hinders regular International Normalized Ratio (INR) monitoring. Novel oral anticoagulants (NOACs) have opened up a new exciting chapter in the field of anticoagulation in non-valvular atrial fibrillation (NVAF). This review discussed the landmark trials that led to the development of NOACs and explored the potentials of these new agents with simultaneous comparison of Warfarin. PMID:27504556

  16. [New oral anticoagulants: recommendations, precautions and perspectives for use].

    PubMed

    Di Minno, Giovanni; Russolillo, Anna; Ventre, Itala; Di Minno, Alessandro; Prisco, Domenico

    2012-11-01

    In phase III studies, some oral inhibitors of both thrombin (dabigatran etexilate) and activated factor X (rivaroxaban, apixaban) have been employed as new anticoagulant drugs in patients with atrial fibrillation or acute coronary syndromes. Such new drugs have overcome a series of limitations of the standard-of-care warfarin, and argue for the possibility of an easy, widespread use of anticoagulation in vascular medicine. However, to this end, we need information on management of bleeding in patients receiving these drugs. Dabigatran etexilate, rivaroxaban and apixaban affect major laboratory tests for clotting. However, at present we do not know whether and how this information may be clinically useful. Their high cost is another major issue, and newer pharmacoeconomic studies are needed to evaluate their cost-effectiveness ratio vs warfarin. PMID:23160017

  17. Factors influencing quality of anticoagulation control and warfarin dosage in patients after aortic valve replacement within the 3 months of follow up.

    PubMed

    Wypasek, E; Mazur, P; Bochenek, M; Awsiuk, M; Grudzien, G; Plincer, D; Undas, A

    2016-06-01

    Warfarin dosage estimation using the pharmacogenetic algorithms has been shown to improve the quality of anticoagulation control in patients with atrial fibrillation. We sought to assess the genetic, demographic and clinical factors that determine the quality of anticoagulation in patients following aortic valve replacement (AVR). We studied 200 consecutive patients (130 men) aged 63 ± 12.3 years, undergoing AVR, in whom warfarin dose was established using a pharmacogenetic algorithm. The quality of anticoagulation within the first 3 months since surgery was expressed as the time of international normalized ratio (INR) in the therapeutic range (TTR). The median TTR in the entire cohort was 59.6% (interquartile range, 38.7 - 82.7). Ninety-nine (49.5%) patients with TTR ≥ 60% did not differ from those with poor anticoagulation control (TTR < 60%) with regard to demographic and cardiovascular risk factors. Coronary artery disease (n = 84, 42%) and previous stroke (n = 5, 2.5%) predicted higher TTR, while possession of CYP2C9*2 variant allele (n = 49, 25%) was associated with lower TTR (P = 0.01). In turn, VKORC1 c.-1639A, CYP2C9*2 and *3 variants were independently associated with actual warfarin dose (P < 0.0001). In AVR patients better anticoagulation control is observed in patients with coronary artery disease and history of stroke, which might result in part from previous lifestyle modification and therapy. Possession of CYP2C9*2 and/or CYP2C9*3 allele variants is associated with lower TTR values and warfarin dose variations in AVR patients, the latter affected also by VKORC1 c.-1693G>A polymorphism. PMID:27511999

  18. Direct oral anticoagulants: a guide for daily practice.

    PubMed

    Fontana, Pierre; Robert-Ebadi, Helia; Bounameaux, Henri; Boehlen, Françoise; Righini, Marc

    2016-01-01

    In recent years, small oral compounds that specifically block activated coagulation factor X (FXa) or thrombin (FIIa) have become alternatives to the anticoagulants that had been used for several decades. As of today, these direct oral anticoagulants (DOACs) include dabigatran etexilate (thrombin inhibitor) and apixaban, edoxaban and rivaroxaban (inhibitors of FXa). While there is no doubt that DOACs represent a major step forward in the management of patients with venous thromboembolic disease and atrial fibrillation, new challenges have arisen. They need to be addressed with the necessary pragmatism on the basis of evidence. Indeed, a better understanding of the management of these last-generation antithrombotics will favour safer use and increase confidence of the practitioner for the prescription of these drugs. The aim of this article is to present practical suggestions for the prescription and use of these drugs in everyday clinical practice, based on clinical experience and recently updated recommendations of the European Heart Rhythm Association and the American College of Chest Physicians among other scientific organisations. We address issues such as pharmacokinetics, dosing, side effects, limitations of use, drug interactions, switching from and to other anticoagulants, renal function, concomitant administration of antiplatelet agents and perioperative use. We also address the issue of monitoring and reversal, taking advantage of the most recent development in this latter area. Rather than being one additional set of recommendations, our narrative review aims at assisting the practicing physician in his or her daily handling of these novel anticoagulant compounds, based on frequently asked questions to the authors, a group of experienced specialists in the field who have, however, no commitment to issue guidelines. PMID:26964028

  19. The Genetic Basis of Resistance to Anticoagulants in Rodents

    PubMed Central

    Pelz, Hans-Joachim; Rost, Simone; Hünerberg, Mirja; Fregin, Andreas; Heiberg, Ann-Charlotte; Baert, Kristof; MacNicoll, Alan D.; Prescott, Colin V.; Walker, Anne-Sophie; Oldenburg, Johannes; Müller, Clemens R.

    2005-01-01

    Anticoagulant compounds, i.e., derivatives of either 4-hydroxycoumarin (e.g., warfarin, bromadiolone) or indane-1,3-dione (e.g., diphacinone, chlorophacinone), have been in worldwide use as rodenticides for >50 years. These compounds inhibit blood coagulation by repression of the vitamin K reductase reaction (VKOR). Anticoagulant-resistant rodent populations have been reported from many countries and pose a considerable problem for pest control. Resistance is transmitted as an autosomal dominant trait although, until recently, the basic genetic mutation was unknown. Here, we report on the identification of eight different mutations in the VKORC1 gene in resistant laboratory strains of brown rats and house mice and in wild-caught brown rats from various locations in Europe with five of these mutations affecting only two amino acids (Tyr139Cys, Tyr139Ser, Tyr139Phe and Leu128Gln, Leu128Ser). By recombinant expression of VKORC1 constructs in HEK293 cells we demonstrate that mutations at Tyr139 confer resistance to warfarin at variable degrees while the other mutations, in addition, dramatically reduce VKOR activity. Our data strongly argue for at least seven independent mutation events in brown rats and two in mice. They suggest that mutations in VKORC1 are the genetic basis of anticoagulant resistance in wild populations of rodents, although the mutations alone do not explain all aspects of resistance that have been reported. We hypothesize that these mutations, apart from generating structural changes in the VKORC1 protein, may induce compensatory mechanisms to maintain blood clotting. Our findings provide the basis for a DNA-based field monitoring of anticoagulant resistance in rodents. PMID:15879509

  20. Tinzaparin reduces health care resource use for anticoagulation in hemodialysis.

    PubMed

    Pettigrew, Martine; Soltys, George I M; Bell, Robert Z; Daniel, Nicole; Davis, Joanne R; Senecal, Lynne; Leblanc, Martine

    2011-04-01

    Anticoagulation is required during hemodialysis to prevent thrombus formation within the extracorporeal circuit. The low-molecular-weight heparin tinzaparin is more expensive than unfractionated heparin (UFH) in Canada but more convenient to administer. We conducted a time-and-motion study to test the hypothesis that tinzaparin may reduce nursing time and total health care costs compared with UFH. Data on health care resource use associated with anticoagulation during hemodialysis for chronic renal failure were collected at an academic hospital in Quebec. Nursing time was recorded for 8 nurses performing 16 dialysis sessions for 4 patients receiving tinzaparin and 4 receiving UFH (2 dialysis sessions per patient). Nurses had ≥ 1 year of experience supervising hemodialysis. We estimated total annual costs of nursing time and health care resources (anticoagulants, medical supplies, and laboratory testing) associated with anticoagulation. In sensitivity analyses, drug costs were varied ± 30% of their base-case values. Estimated annual nursing times per patient were 0.8 vs. 11.5 hours in the first year and 0.6 vs. 10.2 hours in subsequent years for tinzaparin vs. UFH, respectively. Annual drug costs per patient were CAD 898.56 for tinzaparin and 546.75 for UFH. Estimated total annual costs were CAD 1061.03 vs. 1012.71 in the first year and CAD 917.75 vs. 895.23 in subsequent years for tinzaparin vs. UFH, respectively. Use of tinzaparin was cost saving relative to UFH if tinzaparin price was reduced 30%. Most of the price differential between tinzaparin and UFH is offset by substantial time savings to nephrology nurses. PMID:21338468

  1. [From old to new anticoagulants: the role of the biologist].

    PubMed

    Samama, Mm; Depasse, F

    2009-01-01

    Anticoagulant drugs are of great interest to patients and clinical physicians, as well as research scientists. The latter two groups combine their efforts to unravel the related mechanisms of action, as well as means of monitoring and proper dosing. Unfractionated heparin and low molecular weight heparins and vitamin K antagonists have been on board for several decades by now. They act on several clotting factors in certain sequences. Newer drugs, produced by chemical synthesis, act on a more specific target, often factor Xa or factor IIa. These newer anticoagulants have a great convenience in being orally administered and not needing routing laboratory monitoring - which is their main advantage. Hirudine and fondaparinux have been registered for a few years. This year, that is 2008 + 2009, two of these new anticoagulants have been registered and approved for use in Europe and Canada - these are dabigatran etexilate (Pradaxa) and rivaroxaban (Xarelto). Both do not require routine laboratory monitoring. However, coagulation assays for measuring their activity have been studied. A small number of standardized tests should be perfected. PMID:19789124

  2. Strategies for urgent reversal of target-specific oral anticoagulants.

    PubMed

    Davis, Estella M; Uhlmeyer, Erin M; Schmidt, David P; Schardt, Greg L

    2014-12-01

    The direct thrombin inhibitor dabigatran and factor Xa inhibitors rivaroxaban and apixaban are US Food and Drug Administration (FDA)-approved target-specific oral anticoagulants (TSOACs) that have emerged onto the market for use in some indications similar to those for warfarin; in addition, edoxaban is seeking FDA approval. Similar indications include reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation for all 3 agents, for the prevention of deep vein thrombosis that may lead to pulmonary embolism in patients undergoing hip or knee surgery for rivaroxaban and apixaban, and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. As anticoagulants, they are all associated with a risk of bleeding, and, unfortunately, there are no approved antidotes for reversal of these agents. A number of small studies in human subjects and in human/animal models exposed to TSOACs have evaluated the use of activated charcoal, hemodialysis for dabigatran, or clotting factor concentrates for their ability to neutralize the anticoagulant effects or reduce drug concentrations of TSOACs. Clotting factor concentrates that have been used include prothrombin complex concentrates and recombinant factor VII. This review examines studies and case reports evaluating these strategies for expedited or emergent reversal of TSOACs. PMID:25485923

  3. [Influence of anticoagulants on the appearance of chronic subdural hematoma].

    PubMed

    Krupa, Mariusz; Moskała, Marek; Składzień, Tomasz; Grzywna, Ewelina

    2009-01-01

    In recent years in the Department of Neurotraumatology in Cracow it has been noticed the frequent connection between appearance of chronic subdural hematoma (CSDH) and treatment by anticoagulant medications. The aim of this study is to draw attention to the problem of insufficient control of anticoagulants consumption, especially by patients treated for cardiovascular system diseases that increases the risk of bleeding and CSDH development. The paper is based on data from questionnaires that was sent to patients with CSDH, cured in the Department of Neurotraumatology form 2004 to 2005. Analyzed was the group of 51 patients with chronic subdural hematoma; 37 individuals (72.5%) confirmed taking acetylsalicylic acid in the period of 3 months before admission to the Department, 9 (17.6%) patients answered that they were taking low-molecular weight heparin. One patient (1.9%) was taking chronically derivative of cumarin. The authors would inform that anticoagulant treatment might favour increase of chronic subdural hematoma incidence. It's especially important, because the average life expectancy has been prolonged in Poland and there are more people taking acetylsalicylic acid. This can be an epidemiological problem in future. PMID:20043584

  4. Anticoagulant activities of piperlonguminine in vitro and in vivo.

    PubMed

    Lee, Wonhwa; Yoo, Hayoung; Ku, Sae-Kwang; Kim, Jeong Ah; Bae, Jong-Sup

    2013-10-01

    Piperlonguminine (PL), an important component of Piper longum fruits, is known to exhibit anti-hyperlipidemic, anti-platelet and anti-melanogenic activities. Here, the anticoagulant activities of PL were examined by monitoring activated-partial-thromboplastin-time (aPTT), prothrombin-time (PT), and the activities of thrombin and activated factor X (FXa). The effects of PL on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-α (TNF-α) activated HUVECs. The results showed that PL prolonged aPTT and PT significantly and inhibited the activities of thrombin and FXa. PL inhibited the generation of thrombin and FXa in HUVECs. In accordance with these anticoagulant activities, PL prolonged in vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significan- tly decreased by PL. Collectively, our results suggest that PL possesses antithrombotic activities and that the current study could provide bases for the development of new anticoagulant agents. PMID:24148768

  5. Endovascular Embolization of Spontaneous Retroperitoneal Hemorrhage Secondary to Anticoagulant Treatment

    SciTech Connect

    Isokangas, Juha-Matti Peraelae, Jukka M.

    2004-11-15

    The purpose of this study was to report a single hospital's experience of endovascular treatment of patients with retroperitoneal hemorrhage (RPH) secondary to anticoagulant treatment. Ten consecutive patients treated in an intensive care unit and needing blood transfusions due to RPH secondary to anticoagulation were referred for digital subtraction angiography (DSA) to detect the bleeding site(s) and to evaluate the possibilities of treating them by transcatheter embolization. DSA revealed bleeding site(s) in all 10 patients: 1 lumbar artery in 4 patients, 1 branch of internal iliac artery in 3 patients and multiple bleeding sites in 3 patients. Embolization could be performed in 9 of them. Coils, gelatin and/or polyvinyl alcohol were used as embolic agents. Bleeding stopped or markedly decreased after embolization in 8 of the 9 (89%) patients. Four patients were operated on prior to embolization, but surgery failed to control the bleeding in any of these cases. Abdominal compartment syndrome requiring surgical or radiological intervention after embolization developed in 5 patients. One patient died, and 2 had sequelae due to RPH. All 7 patients whose bleeding stopped after embolization had a good clinical outcome. Embolization seems to be an effective and safe method to control the bleeding in patients with RPH secondary to anticoagulant treatment when conservative treatment is insufficient.

  6. Popular naturally occurring antioxidants as potential anticoagulant drugs.

    PubMed

    Bijak, Michal; Saluk, Joanna; Szelenberger, Rafal; Nowak, Pawel

    2016-09-25

    Blood coagulation is a physiological process whose main task is prevention of blood loss from injured vessels. This process consists of a series of zymogens proteolytic activation leading to the generation of the main coagulation enzyme - thrombin. Besides its important role in blood coagulation process, thrombin is involved in many cardiovascular diseases, which are responsible for almost half of fatalities in economically developed countries. The evidence for the increased generation and in vivo activity of thrombin was observed in the plasma of individuals at high risk for clinically significant venous and arterial thromboembolic complications. Antioxidants activity of plants extracts has been well known for many years and was confirmed by many publications. However, during the last decade many research centers presented results suggesting anticoagulant potential of various plant extracts. Many researchers have also provided evidence that polyphenol compounds are able to inhibit the activity of many enzymes, including serine proteases. All research described in this review clearly indicate that polyphenols and polyphenol-rich extracts possess not only antioxidative but also anticoagulant properties and may be useful in creation of new therapeutic agents or dietary supplements. Based on described properties polyphenols would be very helpful with both prevention and treatment of thromboembolic complications associated with multiple failures of haemostasis, because the available therapeutic agents do not offer such double-effects (antioxidant and anticoagulant). PMID:27475864

  7. Anticoagulation After Cardioembolic Stroke: To Bridge or Not to Bridge?

    PubMed Central

    Hallevi, Hen; Albright, Karen C.; Martin-Schild, Sheryl; Barreto, Andrew D.; Savitz, Sean I.; Escobar, Miguel A.; Gonzales, Nicole R.; Noser, Elizabeth A.; Illoh, Kachi; Grotta, James C.

    2009-01-01

    Background Most patients with cardioembolic stroke require long-term anticoagulation. Still, uncertainty exists regarding the best mode of starting long-term anticoagulation. Design, Setting, and Patients We conducted a retrospective review of all patients with cardioembolic stroke admitted to our center from April 1, 2004, to June 30, 2006, and not treated with tissue plasminogen activator. Patients were grouped by treatment: no treatment, aspirin only, aspirin followed by warfarin sodium, intravenous heparin sodium in the acute phase followed by warfarin (heparin bridging), and full-dose enoxaparin sodium combined with warfarin (enoxaparin bridging). Outcome measures and adverse events were collected prospectively. Laboratory values were captured from the records. Main Outcome Measures Symptomatic hemorrhagic transformation, stroke progression, and discharge modified Rankin Scale score. Results Two hundred four patients were analyzed. Recurrent stroke occurred in 2 patients (1%). Progressive stroke was the most frequent serious adverse event, seen in 11 patients (5%). Hemorrhagic transformation occurred in a bimodal distribution—an early benign hemorrhagic transformation and a late symptomatic hemorrhagic transformation. All of the symptomatic hemorrhagic transformation cases were in the enoxaparin bridging group (10%) (P=.003). Systemic bleeding occurred in 2 patients (1%) and was associated with heparin bridging (P=.04). Conclusions Anticoagulation of patients with cardioembolic stroke can be safely started with warfarin shortly after stroke. Heparin bridging and enoxaparin bridging increase the risk for serious bleeding. PMID:18625852

  8. Anticoagulation in chronic kidney disease patients—the practical aspects

    PubMed Central

    Hughes, Stephen; Szeki, Iren; Nash, Michael J.; Thachil, Jecko

    2014-01-01

    There is an increasing awareness about the risks of arterial and venous thromboembolism (TE) in hospital patients and general public which has led to consideration of thrombosis prevention measures in earnest. Early recognition of the symptoms of TE disease has led to timely administration of antiplatelet and anticoagulant drugs, translating to better outcome in many of these patients. In this respect, patients with chronic kidney disease (CKD) represent a special group. They indeed represent a high-risk group for thrombosis both in the cardiovascular territory and also in the venous circulation. At the same time, abnormalities in the platelet membranes put them at risk of bleeding which is significantly more than other patients with chronic diseases. Anticoagulation may be ideal to prevent the former, but the co-existing bleeding risk and also that the commonly used drugs for inhibiting coagulation are eliminated by renal pathways pose additional problems. In this review, we try to explain the complex thrombotic-haemorrhagic state of chronic kidney disease patients, and practical considerations for the management of anticoagulation in them with a focus on heparins. PMID:25878775

  9. Analysis of Clinical Record Data for Anticoagulation Management within an EHR System

    PubMed Central

    Austin, T; Kalra, D; Lea, N.C; Patterson, D.L.H; Ingram, D

    2009-01-01

    Objectives: This paper reports an evaluation of the properties of a generic electronic health record information model that were actually required and used when importing an existing clinical application into a generic EHR repository. Method: A generic EHR repository and system were developed as part of the EU Projects Synapses and SynEx. A Web application to support the management of anticoagulation therapy was developed to interface to the EHR system, and deployed within a north London hospital with five years of cumulative clinical data from the previous existing anticoagulation management application. This offered the opportunity to critique those parts of the generic EHR that were actually needed to represent the legacy data. Results: The anticoagulation records from 3,226 patients were imported and represented using over 900,000 Record Components (i.e. each patient’s record contained on average 289 nodes), of which around two thirds were Element Items (i.e. value-containing leaf nodes), the remainder being container nodes (i.e. headings and sub-headings). Each node is capable of incorporating a rich set of context properties, but in reality it was found that many properties were not used at all, and some infrequently (e.g. only around 0.5% of Record Components had ever been revised). Conclusions: The process of developing generic EHR information models, arising from research and embodied within new-generation interoperability standards and specifications, has been strongly driven by requirements. These requirements have been gathered primarily by collecting use cases and examples from clinical communities, and been added to successive generations of these models. A priority setting approach has not to date been pursued - all requirements have been received and almost invariably met. This work has shown how little of the resulting model is actually needed to represent useful and usable clinical data. A wider range of such evaluations, looking at different

  10. Treatment of experimental mesangioproliferative glomerulonephritis with non-anticoagulant heparin: therapeutic efficacy and safety.

    PubMed

    Burg, M; Ostendorf, T; Mooney, A; Koch, K M; Floege, J

    1997-04-01

    Treatment with conventional heparin is effective in experimental mesangioproliferative glomerulonephritis. However, the long-term effects and safety of this therapy, in particular in the presence of mesangiolysis, have not been assessed. In addition, this therapy has been hampered by bleeding complications. In the present study, therefore, we investigated the long-term effects of a short course of non-anticoagulant (NA) heparin treatment in the anti-Thy 1.1 mesangioproliferative glomerulonephritis, in which early immune-mediated mesangiolysis subsequently leads to mesangial hyperproliferation. Rats received continuous ip NA-heparin or vehicle during the active mesangioproliferative phase (Days 2 to 9; early treatment) or during the early resolution phase (Days 10 to 17; late treatment). Whereas NA-heparin in the early treatment group did not affect the glomerular macrophage, lymphocyte, or platelet influx, it did lead to significantly decreased glomerular cellularity, mesangial cell proliferation, alpha-smooth muscle actin, desmin expression (ie, markers of activated mesangial cells), and matrix accumulation as well as to persistent mesangiolytic lesions including microaneurysms. Despite this latter finding, at Day 120, NA-heparin-treated rats of the early treatment group showed significantly better renal function and less proteinuria and glomerulosclerosis than vehicle-infused rats. In contrast, late therapy with NA-heparin neither accelerated resolution of the nephritis or otherwise affected the course of the disease. We conclude that transient NA-heparin therapy is effective in mesangioproliferative glomerulonephritis, both acutely and long term, when it is initiated during the active phase of the disease. Also, NA-heparin therapy is safe even in glomerular diseases accompanied by mesangiolysis. PMID:9111513

  11. X-ray structures of the anticoagulants coumatetralyl and chlorophacinone. Theoretical calculations and SAR investigations on thirteen anticoagulant rodenticides

    NASA Astrophysics Data System (ADS)

    Dolmella, A.; Gatto, S.; Girardi, E.; Bandoli, G.

    1999-12-01

    Coumatetralyl and chlorophacinone, two substances related to 4-hydroxycoumarin (HC) and to 1,3-indandione (ID), respectively, show activity as anticoagulant rodenticides. In the present study we have investigated the solid-state structures of coumatetralyl and chlorophacinone by means of X-ray single-crystal and powder diffraction, along with thermal analysis. The crystal structures of the two compounds have been used as input geometries for a series of computational chemistry efforts, involving other anticoagulant derivatives as well. Thus, ab initio, semiempirical molecular orbital, molecular mechanics and molecular dynamics/simulated annealing calculations have been performed on thirteen anticoagulant rodenticides. In particular, the annealing calculations have been made to assess the conformational freedom of the compounds under scrutiny. All the generated conformers have been classified into families. The classification has first been made empirically, and then validated by means of a cluster analysis. A number of structural and physico-chemical parameters derived from the calculations has been used in turn for structure-activity relationships (SARs) investigations. In the latter, we have assessed how the selected parameters affect toxicity. The results seem to be consistent with a three-dimensional biophore model, in which higher toxicity is predicted for the more voluminous rodenticides. We suggest that these compounds better fit the active site of the target enzyme vitamin K 2,3-epoxide reductase (KO-reductase).

  12. Genetic testing to guide warfarin dosing: Impact of direct oral anticoagulants.

    PubMed

    Lentz, S R

    2016-08-01

    Despite rapid growth in the use of direct oral anticoagulants (DOACs), warfarin remains a widely prescribed anticoagulant drug. It is likely that the overall use of warfarin will continue to decline, but not completely disappear, as indications for DOACs expand. This changing anticoagulation landscape, along with the likelihood that personalized genomic information will become increasingly available, has several implications for the future of warfarin dosing strategies. PMID:27178490

  13. Anticoagulation to prevent stroke in atrial fibrillation and its implications for managed care.

    PubMed

    Singer, D E

    1998-03-12

    Nonrheumatic atrial fibrillation (AFib) is the most potent common risk factor for stroke, raising the risk of stroke 5-fold. Six randomized trials of anticoagulation in AFib consistently demonstrated a reduction in the risk of stroke by about two-thirds. In these trials, anticoagulation in AFib was quite safe. In contrast, randomized trials indicate that aspirin confers only a small reduction in risk of stroke, at best. Pooled data from the first set of randomized trials indicate that prior stroke, hypertension, diabetes, and increasing age are independent risk factors for future stroke with AFib. Individuals < 65 years old with none of the other risk factors might safely avoid anticoagulation; for all others, anticoagulation seems indicated. Studies of hemorrhagic risk highlight the importance of keeping the international normalized ratio (INR) < 4.0. Recent analyses also reveal that risk of ischemic stroke in AFib increases greatly at INR levels < 2.0. Efficacy and safety of anticoagulation in AFib depend on maintaining the INR between 2.0-3.0. Cost-effectiveness studies indicate that anticoagulation for AFib is among the most efficient preventive interventions in adults. Importantly, the benefits of anticoagulation in AFib accrue immediately. The implications for managed care organizations are that anticoagulation for AFib should be encouraged in their covered populations, and that dedicated anticoagulation services should be developed to promote system-wide control of anticoagulation intensity. Quality measures would include the proportion of patients with AFib who are anticoagulated, and the percentage of time patients' INR levels are between 2.0-3.0. Managed care organizations can benefit from recent research on anticoagulation for AFib; they have a responsibility to support future research and development efforts. PMID:9525571

  14. Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

    PubMed

    Sieg, Adam; Mardis, B Andrew; Mardis, Caitlin R; Huber, Michelle R; New, James P; Meadows, Holly B; Cook, Jennifer L; Toole, J Matthew; Uber, Walter E

    2015-01-01

    Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation. PMID:26273933

  15. Safety of anticoagulation in the treatment of venous thromboembolism in patients with haematological malignancies and thrombocytopenia: Report of 5 cases and literature review.

    PubMed

    Lim, Ming Sheng; Enjeti, Anoop K

    2016-09-01

    Venous thromboembolism (VTE) is relatively common among patients with haematological malignancies. Management is challenging because many of these patients are also thrombocytopenic and at increased risk of bleeding. Current recommendations regarding the treatment of VTE in thrombocytopenic patients with haematological malignancies are limited as there only few studies evaluating the safety and efficacy of anticoagulation in this population of patient. A literature review on the safety of antithrombotic therapy for treatment or prophylaxis of VTE in patients with haematological malignancies was undertaken. This includes a report on 5 patients with haematological malignancies at our institute who received enoxaparin for treatment of VTE while thrombocytopenic. Unlike previous case series which showed that the use of LMWH (low molecular weight heparin) is safe in this group of patients, major bleeding occurred in 2 patients, and was fatal in one case. More studies are required to evaluate the risk factors and safety of anticoagulation in these patients. PMID:27397486

  16. Practical and clinical considerations in assessing patients with atrial fibrillation for switching to non-vitamin K antagonist oral anticoagulants in primary care

    PubMed Central

    Guimarães, Patrícia O; Kaatz, Scott; Lopes, Renato D

    2015-01-01

    Atrial fibrillation (AF) is an important risk factor for thromboembolic events, and anticoagulation therapy can reduce this risk. Vitamin K antagonists (VKAs), such as warfarin, have been used for decades in patients with AF for stroke prevention. Currently, non-VKA oral anticoagulants (NOACs) are approved and available for non-valvular AF patients who are at increased risk of stroke. These agents are safe and effective and have important advantages over VKAs, such as significant reduction in intracranial hemorrhage and no need for routine laboratory monitoring. Thus, should all VKA-treated patients be switched to a NOAC? The aims of this article are: 1) to review the advantages of NOACs over VKAs; 2) to identify the group of patients who most benefit from receiving a NOAC and, therefore, are higher priority to be switched from VKAs; and 3) to provide clinical and practical guidance on how to switch patients safely from VKAs to NOACs. PMID:26379443

  17. Treatment of High-risk Venous Thrombosis Patients Using Low-dose Intraclot Injections of Recombinant Tissue Plasminogen Activator and Regional Anticoagulation

    PubMed Central

    Chang, Richard; Butman, John A.; Lonser, Russell R.; Sherry, Richard M.; Pandalai, Prakash K.; Horne, McDonald K.; Lozier, Jay N.

    2013-01-01

    Seven patients with venous thrombosis and contraindications to traditional thrombolytic therapy, consisting of recent intracranial surgery, recent pineal or retroperitoneal hemorrhage, active genitourinary or gastrointestinal bleeding, epidural procedures, and impending surgery, were successfully treated with a modified thrombolytic regimen. To improve safety, prolonged continuous infusions of tissue plasminogen activator (tPA) was eliminated in favor of once-daily low-dose intraclot injections of tPA to minimize the amount and duration of tPA in the systemic circulation, and low-therapeutic or regional anticoagulation was used to reduce anticoagulant risks. These modifications may allow thrombolytic treatment for selected patients with severe venous thrombosis who are deemed to be at high risk. PMID:23273695

  18. Direct oral anticoagulant use and stent thrombosis following an acute coronary syndrome: A potential new pharmacological option?

    PubMed

    Welsh, Robert C; Zeymer, Uwe; Tarrantini, Giuseppe

    2016-05-01

    With the evolution of techniques and pharmacological strategies in percutaneous coronary intervention, significant advances have been made towards reducing the risk of in-stent restenosis and improving patient outcomes. However, in spite of these advances, stent thrombosis remains a deadly complication of stent implantation. The fundamental challenge in implementing a combined anticoagulant and antiplatelet strategy is balancing the risk of bleeding with the enhanced efficacy of therapy on both pathways. Results from the ATLAS ACS 2-TIMI 51 trial suggest that the addition of rivaroxaban 2.5mg twice daily to standard antiplatelet therapy may achieve this desired balance alongside careful patient selection. This review considers the clinical burden and pathology of stent thrombosis, oral antithrombotic strategies to reduce stent thrombosis, and what findings from recent trials could mean for the long-term management of patients with an acute coronary syndrome. PMID:27020515

  19. Acquired haemophilia masked by warfarin therapy.

    PubMed

    Vadikolia, C M; Riddell, A; Brooks, S; Yee, T T; Brown, S; Lee, C

    2007-02-01

    Acquired haemophilia is a rare phenomenon and prompt diagnosis is essential for successful treatment. Early laboratory detection could minimize its potentially devastating consequences and reduce mortality but when a masking element such as anticoagulant therapy is present, delay in diagnosis is not uncommon. A prolonged activated partial thromboplastin time (APTT) may be falsely attributed to warfarin alone, particularly when it is associated with oral anticoagulant overdose. We describe two patients on treatment with warfarin who presented with a bleeding diathesis and disproportionately prolonged APTT, which led to the diagnosis of antibodies directed against factor VIII. PMID:17224010

  20. [Anti DIC therapy].

    PubMed

    Yahata, Mayuko; Sakamoto, Yuichiro

    2016-02-01

    A variety of disorders erratically activate coagulation cascades. The disseminated intravascular coagulation (DIC) is caused by unbalanced activation between coagulation and fibrinolysis. Some of auxiliary treatments for DIC on top of main therapy against causative disease are beneficial in terms of better outcome. The anticoagulation therapy is indicated when an activation of coagulation dominates in DIC caused by sepsis. Whereas in DIC associated with trauma, since balance between coagulation and fibrinolysis collapses drastically in a short period, both anticoagulantion therapy and antifibrinolytic therapy can be utilized depending on clinical conditions. There are quite a few of anti DIC agents in Japan. It is imperative to choose appropriate agents to treat DIC taking their pharmacological properties into account. PMID:26915249

  1. Evaluation of a Heparin-Calibrated Antifactor Xa Assay for Measuring the Anticoagulant Effect of Oral Direct Xa Inhibitors.

    PubMed

    Beyer, Jacob; Trujillo, Toby; Fisher, Sheila; Ko, Ann; Lind, Stuart E; Kiser, Tyree H

    2016-07-01

    The introduction of oral direct anti-Xa anticoagulants apixaban and rivaroxaban has significantly impacted the treatment and prevention of thromboembolic disease. Clinical scenarios exist in which a quantitative assessment for degree of anticoagulation due to these agents would aid management. The purpose of this work was to evaluate the chromogenic antifactor Xa assay calibrated with heparin standards at our institution for assessment of intensity of anticoagulation with rivaroxaban or apixaban in addition to its current use for unfractionated heparin or low-molecular-weight heparin. We also aimed to propose expected steady state peak and trough antifactor Xa activities for these agents based upon dosing regimens approved for nonvalvular atrial fibrillation. Antifactor Xa activity correlated very strongly with apixaban and rivaroxaban concentration in both spiked samples and treated patient plasma samples (r (2) = .99, P < .001). This correlation was observed over a broad range (20-500 ng/mL) of drug concentrations, as sample dilution with pooled normal plasma significantly extended the range of quantitative assessment. Based on drug concentrations previously published in pharmacokinetic studies, the expected steady state peak and trough antifactor Xa activity ranges for apixaban are 1.80 to 2.20 IU/mL and 0.70 to 1.10 IU/mL, respectively. For rivaroxaban, these ranges are 3.80 to 6.20 IU/mL and 0.60 to 1.00 IU/mL, respectively. In conclusion, our findings demonstrate that heparin-calibrated antifactor Xa activity correlates strongly with apixaban and rivaroxaban concentration. The dilution of samples allowed for this correlation to be extended over the majority of on-therapy drug concentrations. PMID:26842561

  2. Derivation of the non-inferiority margin for the evaluation of direct oral anticoagulants in the treatment of venous thromboembolism

    PubMed Central

    2013-01-01

    Background Direct oral anticoagulants that target a single coagulation factor have been developed as an alternative to standard therapies with heparin and/or vitamin K antagonists. The purpose of this study was to derive non-inferiority margins suitable for randomised clinical studies designed to evaluate these agents for the treatment of venous thromboembolism (VTE). Methods We performed a systematic review to derive non-inferiority margins suitable for use in studies evaluating direct oral anticoagulants for the treatment of VTE. A PubMed search identified publications that evaluated current standard treatment versus placebo, ‘no treatment’ or ‘less intensive treatment’ in patients with symptomatic deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Publications were eligible if they had a randomised study design, included patients with symptomatic DVT and/or PE, used objective diagnostic methods to document the index event and reported objectively confirmed symptomatic recurrent VTE. Results Fourteen publications were included in the analysis. Recurrent VTE occurred in 25 (1.5%) out of 1715 patients who received current standard of care and in 157 (9.2%) out of 1711 patients who received placebo, ‘no treatment’ or ‘less intensive treatment’, for an odds ratio of 0.18 (95% confidence interval, 0.14−0.25; test for heterogeneity, p=0.87). In order to preserve 50% or 75% of the established treatment effect using a linear scale, the corresponding thresholds for non-inferiority equalled 2.50 and 1.75, respectively. Conclusions This systematic review and statistical approach determined non-inferiority margins suitable for use in studies of direct oral anticoagulants for the treatment of DVT and/or PE. PMID:23829521

  3. A new paradigm shift in antithrombotic therapy

    PubMed Central

    Pudusseri, Anita; Shameem, Raji; Spyropoulos, Alex C.

    2013-01-01

    Decades after the introduction of oral anti-coagulants namely the vitamin K antagonist (VKA) Warfarin and antiplatelet agents such as Aspirin and Plavix, new classes of direct, small molecule, novel oral anti-coagulant medications and antiplatelet P2Y12 receptor inhibitors have recently become available. For the novel oral anticoagulants (NOAC), these agents can be separated by direct thrombin inhibitors such as Dabigatran and direct Factor Xa inhibitors such as Rivaroxaban and Apixaban. For next generation antiplatelet agents such as Ticagrelor and Prasugrel, these new P2Y12 receptor inhibitors form the cornerstone of therapy for patients with acute coronary syndrome (ACS) or undergoing percutaneous interventions. These novel oral antithrombotics are revolutionizing the field of stroke prevention, atrial fibrillation (AF), the management of venous thromboembolism (VTE) and treatment of ACS. This article reviews the current research developed in order to identify therapeutic effects and establish net clinical benefits of these new oral antithrombotics. PMID:24155721

  4. Extended Anticoagulant and Aspirin Treatment for the Secondary Prevention of Thromboembolic Disease: A Systematic Review and Meta-Analysis

    PubMed Central

    2015-01-01

    Background Patients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended “life-long” anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a “weak provoking factor” there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event. Objective A systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued. Data Sources MEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles. Study Selection Randomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy. Data Extraction Independent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the

  5. [More with atrial fibrillation, anticoagulants since the coming of NOAK ].

    PubMed

    Forslund, Tomas; von Euler, Mia; Johnsson, Hans; Holmström, Margareta; Wettermark, Björn; Hjemdahl, Paul

    2015-01-01

    Since the introduction of NOAC (non-vitamin K antagonist oral anticoagulants) in 2011 as thromboprophylactic treatment for patients with atrial fibrillation, AF, the number of patients with a diagnosis of atrial fibrillation has increased markedly in our health care registers. The proportion of patients treated with warfarin or NOAC has increased from 47 % to 58 % in 2013. The use of acetylsalicylic acid in patients is decreasing rapidly in patients with AF. NOAC are mostly prescribed by specialists and are mainly used in younger patients with lower CHA2DS2-VASc scores and lower risk for renal insufficiency and bleeding. PMID:25584610

  6. Should we revisit anticoagulation guidelines during thyroid storm?

    PubMed

    Petersen, Andrew W; Puig-Carrión, Gisela D; López-Candales, Angel

    2015-01-01

    Thyroid storm is a rare but potentially catastrophic disease expression of thyrotoxicosis with well-recognized cardiovascular manifestations such as heart failure and atrial fibrillation. Even through some studies have found an increased risk of cardiac thrombus formation and subsequent thromboembolism in these patients, the use of anticoagulation to prevent thromboembolic sequelae of thyrotoxic atrial fibrillation remains unclear. We present a patient presenting with new onset dilated cardiomyopathy and resistant atrial fibrillation with thyroid storm that had a large left atrial appendage clot. Case particulars are discussed and the literature reviewed. PMID:26035989

  7. Phthalide Derivatives with Anticoagulation Activities from Angelica sinensis.

    PubMed

    Zhang, Lai-Bin; Lv, Jie-Li; Liu, Jun-Wei

    2016-07-22

    Two new phthalide derivatives, angesinenolides A and B (1 and 2), were isolated from the roots of Angelica sinensis. Their structures were elucidated using HRMS, NMR, and X-ray crystallographic data. Compound 1 is the first example of a phthalide trimer presumably formed through two [2+2] cycloaddition reactions. Compound 2 is a unique dimeric phthalide with a peroxy bridge between C-3a and C-6. Both phthalides were evaluated for in vitro anticoagulation activities. Compound 1 reduced the level of fibrinogen (FIB). Compound 2 significantly extended thrombin time and activated partial thromboplastin time, as well as markedly reduced the content of FIB. PMID:27400088

  8. Novel oral anticoagulants and reversal agents: Considerations for clinical development.

    PubMed

    Sarich, Troy C; Seltzer, Jonathan H; Berkowitz, Scott D; Costin', James; Curnutte, John T; Gibson, C Michael; Hoffman, Maureane; Kaminskas, Edvardas; Krucoff, Mitchell W; Levy, Jerrold H; Mintz, Paul D; Reilly, Paul A; Sager, Philip T; Singer, Daniel E; Stockbridge, Norman; Weitz, Jeffrey I; Kowey, Peter R

    2015-06-01

    This white paper provides a summary of presentations and discussions that were held at an Anticoagulant-Induced Bleeding and Reversal Agents Think Tank co-sponsored by the Cardiac Safety Research Consortium and the US Food and Drug Administration (FDA) at the FDA's White Oak Headquarters on April 22, 2014. Attention focused on a development pathway for reversal agents for the novel oral anticoagulants (NOACs). This is important because anticoagulation is still widely underused for stroke prevention in patients with atrial fibrillation. Undertreatment persists, although NOACs, in general, overcome some of the difficulties associated with anticoagulation provided by vitamin K antagonists. One reason for the lack of a wider uptake is the absence of NOAC reversal agents. As there are neither widely accepted academic and industry standards nor a definitive regulatory policy on the development of such reversal agents, this meeting provided a forum for leaders in the fields of cardiovascular clinical trials and cardiovascular safety to discuss the issues and develop recommendations. Attendees included representatives from pharmaceutical companies; regulatory agencies; end point adjudication specialist groups; contract research organizations; and active, academically based physicians. There was wide and solid consensus that NOACs overall offer improvements in convenience, efficacy, and safety compared with warfarin, even without reversal agents. Still, it was broadly accepted that it would be helpful to have reversal agents available for clinicians to use. Because it is not feasible to do definitive outcomes studies demonstrating a reversal agent's clinical benefits, it was felt that these agents could be approved for use in life-threatening bleeding situations if the molecules were well characterized preclinically, their pharmacodynamic and pharmacokinetic profiles were well understood, and showed no harmful adverse events in early human testing. There was also consensus

  9. Direct oral anticoagulants: a practical guide for the emergency physician.

    PubMed

    Hogg, Kerstin; Panag, Ajit; Worster, Andrew; Thachil, Jecko

    2016-10-01

    The direct oral anticoagulants (DOACs) are the mainstay for stroke prophylaxis in nonvalvular atrial fibrillation and treatment of acute venous thrombosis. They are attractive alternatives to warfarin because of their efficacy, ease of prescription and safety profile. The emergency department has gained expertise in the management of DOAC bleeding complications, but has been slower to adopt prescription decisions. Emergency clinicians are in a unique position to identify patients who are prescribed DOACs and are at high risk of impending bleeding. This is a practical guide for the emergency clinician on how to prescribe DOACs, the red flags for DOAC patients in the emergency department and advances in the treatment of bleeding. PMID:27116543

  10. Dietary vitamin K guidance: an effective strategy for stable control of oral anticoagulation?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous factors have been identified as risk factors for instability of oral anticoagulation, including variability in vitamin K intake. However few studies have directly tested the feasibility of manipulating dietary vitamin K to achieve stable oral anticoagulation. Recent findings from a rando...

  11. Regional citrate anticoagulation for RRTs in critically ill patients with AKI.

    PubMed

    Morabito, Santo; Pistolesi, Valentina; Tritapepe, Luigi; Fiaccadori, Enrico

    2014-12-01

    Hemorrhagic complications have been reported in up to 30% of critically ill patients with AKI undergoing RRT with systemic anticoagulation. Because bleeding is associated with significantly increased mortality risk, strategies aimed at reducing hemorrhagic complications while maintaining extracorporeal circulation should be implemented. Among the alternatives to systemic anticoagulation, regional citrate anticoagulation has been shown to prolong circuit life while reducing the incidence of hemorrhagic complications and lowering transfusion needs. For these reasons, the recently published Kidney Disease Improving Global Outcomes Clinical Practice Guidelines for Acute Kidney Injury have recommended regional citrate anticoagulation as the preferred anticoagulation modality for continuous RRT in critically ill patients in whom it is not contraindicated. However, the use of regional citrate anticoagulation is still limited because of concerns related to the risk of metabolic complications, the complexity of the proposed protocols, and the need for customized solutions. The introduction of simplified anticoagulation protocols based on citrate and the development of dialysis monitors with integrated infusion systems and dedicated software could lead to the wider use of regional citrate anticoagulation in upcoming years. PMID:24993448

  12. Relationship between diet and anticoagulant response to warfarin – A factor analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diet composition is one of the factors that may contribute to intraindividual variability in the anticoagulant response to warfarin. The aim of this study was to determine the associations between food pattern and anticoagulant response to warfarin in a group of Brazilian patients with vascular dis...

  13. Non-vitamin K antagonist oral anticoagulants and atrial fibrillation guidelines in practice: barriers to and strategies for optimal implementation

    PubMed Central

    Camm, A. John; Pinto, Fausto J.; Hankey, Graeme J.; Andreotti, Felicita; Hobbs, F.D. Richard

    2015-01-01

    Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers. PMID:26116685

  14. Clinical strategies for selecting oral anticoagulants in patients with atrial fibrillation

    PubMed Central

    Sherwood, Matthew W.; Becker, Richard C.

    2014-01-01

    Atrial fibrillation is a common arrhythmia. One of the important aspects of the management of atrial fibrillation is stroke prevention. Warfarin has been the longstanding anticoagulant used for stroke prevention in patients with atrial fibrillation. There are now three novel oral anticoagulants, which have been studied in randomized controlled trials and subsequently approved by the Federal Drug Administration for stroke prevention in patients with atrial fibrillation. Special patient populations, including renal insufficiency, elderly, prior stroke, and extreme body weights, were represented to varying degrees in the clinical trials of the novel oral anticoagulants. Furthermore, there is variation in the pharmacokinetics and pharmacodynamics of each anticoagulant, which affect the patient populations differently. Patients and clinicians are faced with the task of selecting among the available anticoagulants, and this review is designed to be a tool for clinical decision-making. PMID:23846737

  15. Reversal of drug-induced anticoagulation: old solutions and new problems.

    PubMed

    Dzik, Walter Sunny

    2012-05-01

    Anticoagulant drugs are taken by millions of patients throughout the world. Warfarin has been the most widely prescribed anticoagulant for decades. In recent years, new oral anticoagulants have been approved for use, are being positioned as alternatives to warfarin, and represent an enormous market opportunity for pharmaceutical companies. Requests for urgent reversal of anticoagulants are not uncommon especially in the setting of critical bleeding. This review summarizes information on reversal of warfarin by vitamin K, plasma, prothrombin complex concentrates, and recombinant VIIa. In addition, we emphasize the lack of current evidence supporting reversibility of the new oral direct thrombin inhibitors and Factor Xa inhibitors. This review is presented to assist transfusion medicine specialists, hematologists, and other clinicians who prescribe blood components for reversal of drug-induced anticoagulation. PMID:22578371

  16. Use of direct oral anticoagulants with regional anesthesia in orthopedic patients.

    PubMed

    Cappelleri, Gianluca; Fanelli, Andrea

    2016-08-01

    The use of direct oral anticoagulants including apixaban, rivaroxaban, and dabigatran, which are approved for several therapeutic indications, can simplify perioperative and postoperative management of anticoagulation. Utilization of regional neuraxial anesthesia in patients receiving anticoagulants carries a relatively small risk of hematoma, the serious complications of which must be acknowledged. Given the extensive use of regional anesthesia in surgery and the increasing number of patients receiving direct oral anticoagulants, it is crucial to understand the current clinical data on the risk of hemorrhagic complications in this setting, particularly for anesthesiologists. We discuss current data, guideline recommendations, and best practice advice on effective management of the direct oral anticoagulants and regional anesthesia, including in specific clinical situations, such as patients undergoing major orthopedic surgery at high risk of a thromboembolic event, or patients with renal impairment at an increased risk of bleeding. PMID:27290980

  17. Preparation of washed platelets from non-anticoagulated human blood.

    PubMed

    Bowry, S K; Müller-Berghaus, G

    1986-09-15

    Sodium citrate is almost always used to anticoagulate blood for the preparation of washed platelet suspensions. Several adverse effects of citrate on platelet functional responses have been reported. We investigated the extent of activation of platelets and plasmatic coagulation during the preparation of washed platelets from human blood to which no anticoagulant was added. Washed platelets from native blood (PNB) were prepared by passing freshly-drawn human blood rapidly through a mixed Sephadex G-25/G-50 column to remove divalent cations. Gel-filtered blood (GFB), diluted by the elution medium containing 0.35% albumin and 2U/ml apyrase, was obtained within 5 minutes of venepuncture. Using CaCl2, the GFB was found to contain a mean of 1.65 X 10 mM calcium. Fibrinopeptide A measurements indicated less activation of plasmatic coagulation in GFB than in citrated blood. Measurements of beta-thromboglobulin and platelet factor 4 during the various stages of the preparation of PNB showed no platelet activation. No platelet aggregates, as measured by the platelet aggregate ratio method, were observed in GFB. Transmission electron microscopy showed intact discoid platelets similar to those in platelet-rich plasma. The reduced activation of platelets and of plasmatic coagulation was due to the more effective removal of calcium ions from the blood by gel filtration than chelation by citrate. PNB may thus provide a model for studying the requirements for calcium in platelet function in the absence of any citrate-platelet interactions. PMID:2945282

  18. Factor Xa inhibitors--new anticoagulants for secondary haemostasis.

    PubMed

    Perzborn, E

    2009-08-01

    Oral factor Xa (FXa) inhibitors are a promising alternative to current anticoagulants. This paper reviews the latest developments of oral direct FXa inhibitors and focuses on those which have been approved for the prevention of venous thromboembolism (VTE) after total hip or knee replacement or are in advanced development and have passed phase II (proof of principle) testing. The most advanced drugs are apixaban, betrixaban, edoxaban, eribaxaban, rivaroxaban, LY517717, TAK-442, and YM150. Rivaroxaban (Xareltoâ) is the first direct FXa inhibitor which has recently been approved for the prevention of VTE in adult patients after elective hip or knee replacement in several countries, including the European Union and Canada. Rivaroxaban has a flat dose-dependent anticoagulant response with a wide therapeutic window and low potential for drug-drug and drug-food interactions. Rivaroxaban can be given in fixed doses without coagulation monitoring. This review describes the pharmacodynamic and pharmacokinetic profiles and the results of clinical trials with FXa inhibitors in the prevention and treatment of thromboembolic disorders. PMID:19644596

  19. A new peptide (Ruviprase) purified from the venom of Daboia russelii russelii shows potent anticoagulant activity via non-enzymatic inhibition of thrombin and factor Xa.

    PubMed

    Thakur, Rupamoni; Kumar, Ashok; Bose, Biplab; Panda, Dulal; Saikia, Debashree; Chattopadhyay, Pronobesh; Mukherjee, Ashis K

    2014-10-01

    Compounds showing dual inhibition of thrombin and factor Xa (FXa) are the subject of great interest owing to their broader specificity for effective anticoagulation therapy against cardiovascular disorders. This is the first report on the functional characterization and assessment of therapeutic potential of a 4423.6 Da inhibitory peptide (Ruviprase) purified from Daboia russelii russelii venom. The secondary structure of Ruviprase is composed of α-helices (61.9%) and random coils (38.1%). The partial N-terminal sequence (E(1)-V(2)-X(3)-W(4)-W(5)-W(6)-A(7)-Q(8)-L(9)-S(10)) of Ruviprase demonstrated significant similarity (80.0%) with an internal sequence of apoptosis-stimulating protein reported from the venom of Ophiophagus hannah and Python bivittatus; albeit Ruviprase did not show sequence similarity with existing thrombin/FXa inhibitors, suggesting its uniqueness. Ruviprase demonstrated a potent in vitro anticoagulant property and inhibited both thrombin and FXa following slow binding kinetics. Ruviprase inhibited thrombin by binding to its active site via an uncompetitive mechanism with a Ki value and dissociation constant (KD) of 0.42 μM and 0.46 μM, respectively. Conversely, Ruviprase demonstrated mixed inhibition (Ki = 0.16 μM) of FXa towards its physiological substrate prothrombin. Furthermore, the biological properties of Ruviprase could not be neutralized by commercial polyvalent or monovalent antivenom. Ruviprase at a dose of 2.0 mg/kg was non-toxic and showed potent in vivo anticoagulant activity after 6 h of intraperitoneal treatment in mice. Because of the potent anticoagulant property as well as non-toxic nature of Ruviprase, the possible application of the peptide as an antithrombotic agent for combating thrombosis-associated ailments appears promising. PMID:25038567

  20. Antithrombotic Therapy for VTE Disease

    PubMed Central

    Kearon, Clive; Comerota, Anthony J.; Prandoni, Paolo; Bounameaux, Henri; Goldhaber, Samuel Z.; Nelson, Michael E.; Wells, Philip S.; Gould, Michael K.; Dentali, Francesco; Crowther, Mark; Kahn, Susan R.

    2012-01-01

    Background: This article addresses the treatment of VTE disease. Methods: We generated strong (Grade 1) and weak (Grade 2) recommendations based on high-quality (Grade A), moderate-quality (Grade B), and low-quality (Grade C) evidence. Results: For acute DVT or pulmonary embolism (PE), we recommend initial parenteral anticoagulant therapy (Grade 1B) or anticoagulation with rivaroxaban. We suggest low-molecular-weight heparin (LMWH) or fondaparinux over IV unfractionated heparin (Grade 2C) or subcutaneous unfractionated heparin (Grade 2B). We suggest thrombolytic therapy for PE with hypotension (Grade 2C). For proximal DVT or PE, we recommend treatment of 3 months over shorter periods (Grade 1B). For a first proximal DVT or PE that is provoked by surgery or by a nonsurgical transient risk factor, we recommend 3 months of therapy (Grade 1B; Grade 2B if provoked by a nonsurgical risk factor and low or moderate bleeding risk); that is unprovoked, we suggest extended therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high (Grade 1B); and that is associated with active cancer, we recommend extended therapy (Grade 1B; Grade 2B if high bleeding risk) and suggest LMWH over vitamin K antagonists (Grade 2B). We suggest vitamin K antagonists or LMWH over dabigatran or rivaroxaban (Grade 2B). We suggest compression stockings to prevent the postthrombotic syndrome (Grade 2B). For extensive superficial vein thrombosis, we suggest prophylactic-dose fondaparinux or LMWH over no anticoagulation (Grade 2B), and suggest fondaparinux over LMWH (Grade 2C). Conclusion: Strong recommendations apply to most patients, whereas weak recommendations are sensitive to differences among patients, including their preferences. PMID:22315268

  1. Periprocedural management of patients receiving a vitamin K antagonist or a direct oral anticoagulant requiring an elective procedure or surgery.

    PubMed

    Spyropoulos, A C; Al-Badri, A; Sherwood, M W; Douketis, J D

    2016-05-01

    The periprocedural management of patients receiving chronic therapy with oral anticoagulants (OACs), including vitamin K antagonists (VKAs) such as warfarin and direct OACs (DOACs), is a common clinical problem. The optimal perioperative management of patients receiving chronic OAC therapy is anchored on four key principles: (i) risk stratification of patient-related and procedure-related risks of thrombosis and bleeding; (ii) the clinical consequences of a thrombotic or bleeding event; (iii) discontinuation and reinitiation of OAC therapy on the basis of the pharmacokinetic properties of each agent; and (iv) whether aggressive management such as the use of periprocedural heparin bridging has advantages for the prevention of postoperative thromboembolism at the cost of a possible increase in bleeding risk. Recent data from randomized trials in patients receiving VKAs undergoing pacemaker/defibrillator implantation or using heparin bridging therapy for elective procedures or surgeries can now inform best practice. There are also emerging data on periprocedural outcomes in the DOAC trials for patients with non-valvular atrial fibrillation. This review summarizes the evidence for the periprocedural management of patients receiving chronic OAC therapy, focusing on recent randomized trials and large outcome studies, to address three key clinical scenarios: (i) can OAC therapy be safely continued for minor procedures or surgeries; (ii) if therapy with VKAs (especially warfarin) needs to be temporarily interrupted for an elective procedure/surgery, is heparin bridging necessary; and (iii) what is the optimal periprocedural management of the DOACs? In answering these questions, we aim to provide updated clinical guidance for the periprocedural management of patients receiving VKA or DOAC therapy, including the use of heparin bridging. PMID:26988871

  2. Acquired hemophilia masked by warfarin therapy: report on two cases.

    PubMed

    Uggla, Bertil; Linder, Olle; Schulman, Sam

    2003-12-01

    Spontaneous appearance of acquired anticoagulants is a rare phenomenon. We present two cases, where such antibodies against factor VIII were masked by warfarin therapy. The two patients were anticoagulated with warfarin due to mechanical heart valve and recurrent thromboembolic events, respectively. Different therapies against the inhibitor of factor VIII were used in the two cases. One patient received corticosteroids and high-dose gammaglobulin with temporary effect and was then effectively treated with cyclophosphamide. The other patient was successfully treated with cyclosporine. The special problems of keeping the balance between thrombosis and bleeding in this group of patients with need of anticoagulation due to mechanical heart valves or other thrombogenic factors are discussed. PMID:14614359

  3. The factor XIIa blocking antibody 3F7: a safe anticoagulant with anti-inflammatory activities.

    PubMed

    Worm, Marie; Köhler, Elodie C; Panda, Rachita; Long, Andy; Butler, Lynn M; Stavrou, Evi X; Nickel, Katrin F; Fuchs, Tobias A; Renné, Thomas

    2015-10-01

    The plasma protein factor XII (FXII) is the initiating protease of the procoagulant and proinflammatory contact system. FXII activates both the bradykinin (BK) producing kallikrein-kinin system and the intrinsic pathway of coagulation. Contact with negatively charged surfaces induces auto-activation of zymogen FXII that results in activated FXII (FXIIa). Various in vivo activators of FXII have been identified including heparin, misfolded protein aggregates, nucleic acids and polyphosphate. Murine models have established a central role of FXII in arterial and venous thromboembolic diseases. Despite the central function of FXII in pathologic thrombosis, its deficiency does not impair hemostasis in animals or humans. The selective role of FXIIa in thrombosis, but not hemostasis, offers an exciting novel strategy for safe anticoagulation based on interference with FXIIa. We have generated the recombinant fully human FXIIa-blocking antibody 3F7, which abolished FXIIa enzymatic activity and prevented thrombosis in a cardiopulmonary bypass system in large animals, in the absence of increased therapy-associated bleeding. Furthermore, 3F7 also interfered with BK-driven edema in the severe swelling disorder hereditary angioedema (HAE) type III. Taken together, targeting FXIIa with 3F7 appears to be a promising approach to treat edema disorders and thrombosis. PMID:26605293

  4. The factor XIIa blocking antibody 3F7: a safe anticoagulant with anti-inflammatory activities

    PubMed Central

    Worm, Marie; Köhler, Elodie C.; Panda, Rachita; Long, Andy; Butler, Lynn M.; Stavrou, Evi X.; Nickel, Katrin F.; Fuchs, Tobias A.

    2015-01-01

    The plasma protein factor XII (FXII) is the initiating protease of the procoagulant and proinflammatory contact system. FXII activates both the bradykinin (BK) producing kallikrein-kinin system and the intrinsic pathway of coagulation. Contact with negatively charged surfaces induces auto-activation of zymogen FXII that results in activated FXII (FXIIa). Various in vivo activators of FXII have been identified including heparin, misfolded protein aggregates, nucleic acids and polyphosphate. Murine models have established a central role of FXII in arterial and venous thromboembolic diseases. Despite the central function of FXII in pathologic thrombosis, its deficiency does not impair hemostasis in animals or humans. The selective role of FXIIa in thrombosis, but not hemostasis, offers an exciting novel strategy for safe anticoagulation based on interference with FXIIa. We have generated the recombinant fully human FXIIa-blocking antibody 3F7, which abolished FXIIa enzymatic activity and prevented thrombosis in a cardiopulmonary bypass system in large animals, in the absence of increased therapy-associated bleeding. Furthermore, 3F7 also interfered with BK-driven edema in the severe swelling disorder hereditary angioedema (HAE) type III. Taken together, targeting FXIIa with 3F7 appears to be a promising approach to treat edema disorders and thrombosis. PMID:26605293

  5. Silent atrial fibrillation as a stroke risk factor and anticoagulation indication.

    PubMed

    Glotzer, Taya V; Ziegler, Paul D

    2013-07-01

    The term "silent" atrial fibrillation (AF) has recently re-emerged to describe atrial arrhythmias that are detected by implanted cardiac devices but would generally go undetected in the clinical setting. The precise role that silent AF plays in increasing the risk of ischemic stroke is not fully understood. The purpose of this article is to: (1) review the current evidence demonstrating that silent AF is associated with thromboembolic events; (2) describe the temporal proximity of silent AF episodes to thromboembolic events; (3) present data on the incidence of newly detected silent AF in patients without a previous history of AF; and (4) provide an overview of ongoing and new clinical studies on this important topic. The current evidence suggests that the prevalence of silent AF is considerable among patients with implanted devices, and that the presence of silent AF increases the risk of thromboembolism. The AF burden threshold which confers this increased thromboembolism risk is not precisely defined, but might be as brief as several minutes to several hours. The advent of novel oral anticoagulation medications, which offer the promise of improved efficacy along with superior safety profiles, might warrant more aggressive identification of patients who might benefit from these therapies. However, to find high risk patients who have brief episodes of silent AF will likely require new methods of monitoring to permit the detection of this elusive but potentially dangerous arrhythmia. PMID:23790594

  6. [ST-segment elevation myocardial infarction in a patient with thrombophilia taking new oral anticoagulants].

    PubMed

    Li Calzi, Mauro; Placci, Angelo; Lina, Daniela; Grassi, Francesca; Paoli, Giorgia; Bianconcini, Michele; Cattabiani, Maria Alberta; Menozzi, Alberto

    2016-06-01

    We report the case of a 65--year-old woman admitted for inferior ST-segment elevation myocardial infarction complicated by complete atrioventricular block. The patient was under treatment with a novel oral anticoagulant (NOAC, rivaroxaban) because of a history of recurrent idiopathic pulmonary embolism. Emergency angiography showed complete acute thrombotic occlusion of the right coronary artery. After manual thrombectomy, there was no angiographic evidence of underlying atherosclerosis, therefore no further percutaneous coronary intervention was performed. Subsequent clinical course was uneventful. Laboratory tests demonstrated the presence of a heterozygous mutation of the factor II gene (G20210A), confirming the clinical evidence of a thrombophilic state. As rivaroxaban seemed to be ineffective in preventing spontaneous coronary thrombosis in this patient, antithrombotic therapy was shifted to warfarin plus low-dose aspirin. No further ischemic events occurred during the 1-year follow-up. It can be hypothesized that factor Xa inhibition by NOACs, such as rivaroxaban, could be insufficient in case of a thrombophilic state due to thrombin mutation. A brief review of the current literature on use of NOACs in acute coronary syndromes is also reported. PMID:27384603

  7. Longest Event-Free Survival without Anticoagulation in a Mechanical Aortic Valve Replacement.

    PubMed

    Salmane, Chadi; Pandya, Bhavi; Lafferty, Kristen; Patel, Nileshkumar J; McCord, Donald

    2016-01-01

    Sixty percent of the patients going for valve replacement opt for mechanical valves and the remaining 40% choose bioprosthetics. Mechanical valves are known to have a higher risk of thrombosis; this risk further varies depending on the type of valve, its position, and certain individual factors. According to current guidelines, long-term anticoagulation is indicated in patients with metallic prosthetic valve disease. We report two unique cases of patients who survived 27 and 37 years event free, respectively, after mechanical aortic valve replacement (AVR) without being on any form of anticoagulation. The latter case described the longest survival in a human with a prosthetic aortic valve without anticoagulation. A review of literature demonstrated few cases of prosthetic valves with no anticoagulation in the long term without significant embolic events reported as case reports. These cases have been summarized in this article. Some cases of long-term survival (in the absence of anticoagulation) were attributed to good luck, and others as the result of genetic variations. New mechanical prosthetic valves can be promising, such as microporus-surfaced valves that may be used without full anticoagulation. The use of dual antiplatelet agents alone can be currently recommended only when a patient cannot take oral anticoagulation after AVR, and it should be followed with measuring and monitoring of platelet reactivity. PMID:27053922

  8. Longest Event-Free Survival without Anticoagulation in a Mechanical Aortic Valve Replacement

    PubMed Central

    Salmane, Chadi; Pandya, Bhavi; Lafferty, Kristen; Patel, Nileshkumar J; McCord, Donald

    2016-01-01

    Sixty percent of the patients going for valve replacement opt for mechanical valves and the remaining 40% choose bioprosthetics. Mechanical valves are known to have a higher risk of thrombosis; this risk further varies depending on the type of valve, its position, and certain individual factors. According to current guidelines, long-term anticoagulation is indicated in patients with metallic prosthetic valve disease. We report two unique cases of patients who survived 27 and 37 years event free, respectively, after mechanical aortic valve replacement (AVR) without being on any form of anticoagulation. The latter case described the longest survival in a human with a prosthetic aortic valve without anticoagulation. A review of literature demonstrated few cases of prosthetic valves with no anticoagulation in the long term without significant embolic events reported as case reports. These cases have been summarized in this article. Some cases of long-term survival (in the absence of anticoagulation) were attributed to good luck, and others as the result of genetic variations. New mechanical prosthetic valves can be promising, such as microporus-surfaced valves that may be used without full anticoagulation. The use of dual antiplatelet agents alone can be currently recommended only when a patient cannot take oral anticoagulation after AVR, and it should be followed with measuring and monitoring of platelet reactivity. PMID:27053922

  9. Concentrations of anticoagulant rodenticides in stoats Mustela erminea and weasels Mustela nivalis from Denmark.

    PubMed

    Elmeros, Morten; Christensen, Thomas Kjær; Lassen, Pia

    2011-05-15

    Anticoagulant rodenticides are widely used to control rodent populations but they also pose a risk of secondary poisoning in non-target predators. Studies on anticoagulant rodenticide exposure of non-target species have mainly reported on frequency of occurrence. They have rarely analyzed variations in residue concentrations. We examine the occurrence and concentrations of five anticoagulant rodenticides in liver tissue from 61 stoats (Mustela erminea) and 69 weasels (Mustela nivalis) from Denmark. Anticoagulant rodenticides were detected in 97% of stoats and 95% of weasels. 79% of the animals had detectable levels of more than one substance. Difenacoum had the highest prevalence (82% in stoats and 88% in weasels) but bromadiolone was detected in the highest concentrations in both stoat (1.290 μg/g ww) and weasel (1.610 μg/g ww). Anticoagulant rodenticide concentrations were highest during autumn and winter and varied with sampling method. Anticoagulant rodenticide concentrations were higher in stoats and weasels with unknown cause of death than in specimens killed by physical trauma. There was a negative correlation between anticoagulant rodenticide concentrations and body condition. Our results suggest that chemical rodent control in Denmark results in an extensive exposure of non-target species and may adversely affect the fitness of some stoats and weasels. PMID:21477845

  10. Differential Kinetics of Coagulation Factors and Natural Anticoagulants in Patients with Liver Cirrhosis: Potential Clinical Implications

    PubMed Central

    Tischendorf, Michael; Miesbach, Wolfgang; Chattah, Umer; Chattah, Zenab; Maier, Sebastian; Welsch, Christoph; Zeuzem, Stefan; Lange, Christian M.

    2016-01-01

    Background Advanced liver diseases are associated with profound alterations of the coagulation system increasing the risk not only of bleeding, but also of thromboembolic complications. A recent milestone study has shown that prophylactic anticoagulation in liver cirrhosis patients results in a reduced frequency of hepatic decompensation. Yet, INR measurement, one of the most widely applied tests to assess liver function, only inaccurately predicts the risk of hepatic decompensation related to alterations of the coagulation system. To assess the relationship between selected coagulation factors / natural anticoagulants with INR, MELD score, and hepatic decompensation, we performed the present pilot study. A total number of 92 patients with various stages of liver cirrhosis were included and prospectively followed for at least 6 months. We found that important natural anticoagulants, namely antithrombin and protein C, as well as factor XI (which may also serve as an anticoagulant) decreased earlier and by a larger magnitude than one would expect from classical coagulation test results. The correlation between these factors and INR was only moderate. Importantly, reduced plasma activities of natural anticoagulants but not INR or MELD score were independent predictors of hepatic encephalopathy (P = 0.013 and 0.003 for antithrombin and protein C, respectively). Conclusion In patients with liver cirrhosis plasma activities of several natural anticoagulants are earlier and stronger affected than routine coagulation tests. Reduced activities of natural anticoagulants may be predictive for the development of hepatic encephalopathy. PMID:27171213

  11. Spontaneous Subcapsular Renal Hematoma: Strange Case in an Anticoagulated Patient with HWMH after Aortic and Iliac Endovascular Stenting Procedure

    PubMed Central

    Greco, Michele; Benedetto, Filippo; Spinelli, Francesco; Traxer, Olivier; Tefik, Tzevat; Pappalardo, Rosa

    2016-01-01

    Spontaneous subcapsular renal hematoma is a rare condition in clinical practice. It is caused by renal cysts, benign and malignant renal tumors, vascular lesions, and antiplatelet or anticoagulant therapy. In this paper we report an unusual case of rupture of a renal cyst of a 66-year-old male patient during an aortic and iliac endovascular procedure for a massive calcified atheroma above the iliac bifurcation. We suspected that the bolus of high weight molecular heparin given during the procedure caused the rupture of the cyst. According to the literature, this is the first case of renal cyst rupture during an endovascular aortic procedure after administering a high weight molecular heparin bolus. PMID:27579210

  12. Spontaneous Subcapsular Renal Hematoma: Strange Case in an Anticoagulated Patient with HWMH after Aortic and Iliac Endovascular Stenting Procedure.

    PubMed

    Greco, Michele; Butticè, Salvatore; Benedetto, Filippo; Spinelli, Francesco; Traxer, Olivier; Tefik, Tzevat; Pappalardo, Rosa; Magno, Carlo

    2016-01-01

    Spontaneous subcapsular renal hematoma is a rare condition in clinical practice. It is caused by renal cysts, benign and malignant renal tumors, vascular lesions, and antiplatelet or anticoagulant therapy. In this paper we report an unusual case of rupture of a renal cyst of a 66-year-old male patient during an aortic and iliac endovascular procedure for a massive calcified atheroma above the iliac bifurcation. We suspected that the bolus of high weight molecular heparin given during the procedure caused the rupture of the cyst. According to the literature, this is the first case of renal cyst rupture during an endovascular aortic procedure after administering a high weight molecular heparin bolus. PMID:27579210

  13. Activated protein C protects against renal ischaemia/reperfusion injury, independent of its anticoagulant properties.

    PubMed

    Lattenist, Lionel; Jansen, Marcel P B; Teske, Gwendoline; Claessen, Nike; Meijers, Joost C M; Rezaie, Alireza R; Esmon, Charles T; Florquin, Sandrine; Roelofs, Joris J T H

    2016-07-01

    Acute renal failure, a serious condition characterised by a drastic decline in renal function, often follows ischaemia/reperfusion (I/R) episodes. I/R is characterised by necrosis, inflammation and activation of coagulation, in concert causing renal tissue damage. In this context, activated protein C (APC) might be of importance in the pathogenesis of renal I/R. APC is a serine protease which has anticoagulant but also several anti-inflammatory and cytoprotective effects such as protection of endothelial barrier function. It was our objective to study the role of cytoprotective and anticoagulant functions of APC during renal I/R. C57BL/6j mice subjected to renal I/R were treated with intraperitoneally injected exogenous human APC, or two mutant forms of APC (200 µg/kg) which specifically lack anticoagulant or signalling properties. In a different experiment mice received specific monoclonal antibodies (20 mg/kg) that block the cytoprotective and/or anticoagulant properties of endogenous APC. Treatment with APC reduced tubular injury and enhanced renal function without altering the inflammatory response and did reduce renal fibrin deposition. Administration of APC mutant lacking anticoagulant properties reduced renal damage and enhanced renal function. Blocking the anticoagulant and cytoprotective functions of endogenous APC resulted in elevated tubular damage and reduced tubular cell proliferation, however, without influencing renal function or the inflammatory response. Furthermore, blocking both the anticoagulant and cytoprotective effects of APC resulted in dramatic renal interstitial haemorrhage, indicative of impaired vascular integrity. Blocking only the anticoagulant function of APC did not result in interstitial bleeding. In conclusion, the renoprotective effect of APC during I/R is independent of its anticoagulant properties. PMID:27052416

  14. Effects of pelletized anticoagulant rodenticides on California quail

    USGS Publications Warehouse

    Blus, L.J.; Henny, C.J.; Grove, R.A.

    1985-01-01

    A moribund, emaciated California quail (Callipepla californica) that was found in an orchard in the state of Washington had an impacted crop and gizzard. Pellets containing the anticoagulant chlorophacinone (Rozol, RO) were in the crop; the gizzard contents consisted of a pink mass of paraffin that was selectively accumulated from the paraffinized pellets. The plasma prothrombin time of 28 sec was near that determined for control quail. The signs of RO intoxication seen in the moribund wild quail were duplicated in captive quail given ad libitum diets of either RO or another paraffinized chlorophacinone pellet (Mr. Rat Guard II, MRG). This left little doubt that paraffin impaction of the gizzard was the primary problem. All captive quail fed RO or MRG pellets showed no increases in prothrombin times compared to control values, died in an emaciated condition, and had gizzards impacted with paraffin.

  15. Novel oral anticoagulants in patients undergoing cardioversion for atrial fibrillation.

    PubMed

    Briasoulis, Alexandros; Kottam, Anupama; Khan, Mazhar; Afonso, Luis

    2015-08-01

    Recent trials on novel oral anticoagulants (NOAC) in patients undergoing cardioversion showed that NOACs are as safe and effective as treatment with vitamin K antagonists in patients with atrial fibrillation undergoing electric or pharmacological cardioversion. We conducted an EMBASE and MEDLINE search for studies in which patients undergoing cardioversion were assigned to treatment with NOACs versus VKAs. We identified one prospective randomized study and three post hoc analysis of randomized trials which enrolled 2,788 controls that received NOACs and 1,729 patients that received VKAs. NOACs and VKAs had comparable effects on the rates of stroke/thromboembolism, major bleeding events and all-cause mortality. NOACs are safe and effective alternatives to VKA in patients with AF undergoing cardioversion. PMID:25542262

  16. Recent developments in the use of oral anticoagulants.

    PubMed

    Lassen, Michael R

    2009-08-01

    For many years, vitamin K antagonists, unfractionated heparins, low-molecular-weight heparins and a pentasaccharide were the only anticoagulant drugs available for the prevention of venous thromboembolism after surgery. However, their benefits were associated with disadvantages, such as their subcutaneous route of administration or the need for coagulation monitoring. Research was challenged to develop new drugs that would simplify thromboprophylaxis while showing equivalent or better efficacy. Rivaroxaban and dabigatran are now available in some countries for the prevention of venous thromboembolism after total hip or knee replacement in adults. Apixaban is also undergoing trials for this indication. Additionally, these drugs show potential for stroke prevention in atrial fibrillation, treatment of venous thromboembolism and prevention of secondary events in acute coronary syndrome. PMID:19548861

  17. Lumbar puncture in patients using anticoagulants and antiplatelet agents.

    PubMed

    Domingues, Renan; Bruniera, Gustavo; Brunale, Fernando; Mangueira, Cristóvão; Senne, Carlos

    2016-08-01

    The use of anticoagulants and antiplatelet agents has largely increased. Diagnostic lumbar puncture in patients taking these drugs represents a challenge considering the opposing risks of bleeding and thrombotic complications. To date there are no controlled trials, specific guidelines, nor clear recommendations in this area. In the present review we make some recommendations about lumbar puncture in patients using these drugs. Our recommendations take into consideration the pharmacology of these drugs, the thrombotic risk according to the underlying disease, and the urgency in cerebrospinal fluid analysis. Evaluating such information and a rigorous monitoring of neurological symptoms after lumbar puncture are crucial to minimize the risk of hemorrhage associated neurological deficits. An individualized patient decision-making and an effective communication between the assistant physician and the responsible for conducting the lumbar puncture are essential to minimize potential risks. PMID:27556380

  18. Treating pulmonary embolism in Pacific Asia with direct oral anticoagulants.

    PubMed

    Cohen, Alexander; Jeyaindran, Sinnadurai; Kim, Jae Yeol; Park, Kihyuk; Sompradeekul, Suree; Tambunan, Karmel L; Tran, Huyen; Tsai, I-Chen; Ward, Christopher; Wong, Raymond

    2015-08-01

    Pulmonary embolism (PE) is the principal preventable cause of in-hospital deaths. Prevalence of PE in Asians is uncertain but undoubtedly underestimated. Asians and Caucasians have similar non-genetic risk factors for PE, and there is mounting evidence that PE affects Asians much more commonly than previously supposed; incidence, especially among high-risk patients, may approach that in Caucasians. Furthermore, PE incidence in Asia is increasing, due to both increased ascertainment, and also population ageing and growing numbers of patients with predisposing risk factors. Despite being warranted, thromboprophylaxis for high-risk patients is not routine in Pacific Asian countries/regions. There also appears to be scope to implement venous thromboembolism (VTE) management guidelines more assiduously. Anticoagulants, primarily heparins and warfarin, have been the mainstays of VTE management for years; however, these agents have limitations that complicate routine use. The complexity of current guidelines has been another barrier to applying evidence-based recommendations in everyday practice. Updated management approaches have considerable potential to improve outcomes. New oral anticoagulants that are easier to administer, require no, or much less, monitoring or dose-adjustment and have a favourable risk/benefit profile compared with conventional modalities, may offer an alternative with the potential to simplify VTE management. However, more information is required on practical management and the occurrence and treatment of bleeding complications. Increasing recognition of the burden of PE and new therapeutic modalities are altering the VTE management landscape in Pacific Asia. Consequently, there is a need to further raise awareness and bridge gaps between the latest evidence and clinical practice. PMID:26139085

  19. Exposure pathways of anticoagulant rodenticides to nontarget wildlife.

    PubMed

    Elliott, John E; Hindmarch, Sofi; Albert, Courtney A; Emery, Jason; Mineau, Pierre; Maisonneuve, France

    2014-02-01

    Second-generation anticoagulant rodenticides are widely reported to contaminate and poison nontarget wildlife, primarily predatory birds and mammals. Exposure pathways, however, have not been well defined. Here, we examined potential movement of rodenticides from deployment of bait to exposure of small mammals and other biota. At two adjacent working farms, we placed baits containing either brodifacoum or bromadiolone. We monitored movement of those compounds to the surrounding environment by collecting small mammals, birds, and invertebrates. Similar collections were made at a third agricultural setting without active bait deployment, but located among intensive livestock production and regular rodenticide use by farmers. Livers and whole invertebrate samples were analyzed for rodenticides using a sensitive LC-MSMS method. Norway rats (Rattus norvegicus) from both baited and non-baited farms had residues of brodifacoum or bromadiolone, implicating rats as an important exposure pathway to wildlife. Among 35 analyzed nontarget small mammals, a single vole had high hepatic residues (18.6 μ/g), providing some indication of a small mammal pathway. One song sparrow (Melospiza melodia) sample from a baited farm contained 0.073 μg/g of brodifacoum in liver, while 0.39 μg/g of diphacinone was measured in a pool of carrion beetles (Dermestes spp.) from the non-baited farm area, implicating avian and invertebrate components in exposure pathways. Regurgitated pellets of barn owl (Tyto alba) selected randomly from baited farms contained no detectable rodenticide residues, while 90% of owl pellets collected from a variety of farms, and selected for the presence of rat fur, contained detectable anticoagulant residues. We recorded behavior of a captive sample of a representative songbird, the house sparrow (Passer domesticus); they readily entered bait stations and fed on (unloaded) bait. PMID:24048882

  20. Chemically sulfated natural galactomannans with specific antiviral and anticoagulant activities.

    PubMed

    Muschin, Tegshi; Budragchaa, Davaanyam; Kanamoto, Taisei; Nakashima, Hideki; Ichiyama, Koji; Yamamoto, Naoki; Shuqin, Han; Yoshida, Takashi

    2016-08-01

    Naturally occurring galactomannans were sulfated to give sulfated galactomannans with degrees of substitution of 0.7-1.4 per sugar unit and molecular weights of M¯n=0.6×10(4)-2.4×10(4). Sulfated galactomannans were found to have specific biological activities in vitro such as anticoagulant, anti-HIV and anti-Dengue virus activities. The biological activities were compared with those of standard dextran and curdlan sulfates, which are polysaccharides with potent antiviral activity and low cytotoxicity. It was found that sulfated galactomannans had moderate to high anticoagulant activity, 13.4-36.6unit/mg, compared to that of dextran and curdlan sulfates, 22.7 and 10.0unit/mg, and high anti-HIV and anti-Dengue virus activities, 0.04-0.8μg/mL and 0.2-1.1μg/mL, compared to those curdlan sulfates, 0.1μg/mL, respectively. The cytotoxicity on MT-4 and LCC-MK2 cells was low. Surface plasmon resonance (SPR) of sulfated galactomannans revealed strong interaction with poly-l-lysine as a model compound of virus proteins, and suggested that the specific biological activities might originate in the electrostatic interaction of negatively charged sulfate groups of sulfated galactomannans and positively charged amino groups of surface proteins of viruses. These results suggest that sulfated galactomannans effectively prevented the infection of cells by viruses and the degree of substitution and molecular weights played important roles in the biological activities. PMID:27154517

  1. Where do we go from here? Reappraising the data on anticoagulation in pulmonary arterial hypertension

    PubMed Central

    Cirulis, Meghan M.

    2016-01-01

    The use of anticoagulation as part of the treatment regimen in pulmonary arterial hypertension (PAH) remains a topic of debate. A recently published analysis of anticoagulation use in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) study offers conflicting conclusions regarding the benefit of this therapeutic strategy. There remains no robust randomized trial in PAH weighing the risks versus benefits of including anticoagulation in treatment regimens, leaving clinicians to surmise value in individual patients. Reexamination of available data may help to p